CHAPTER 14

Beyond the Stress Concept: Allostatic

Load—A Developmental Biological and
Cognitive Perspective
SONIA J. LUPIEN, ISABELLE OUELLET-MORIN, ALMUT HUPBACH, MAI T. TU, CLAUDIA BUSS,
DOMINIQUE WALKER, JENS PRUESSNER, and BRUCE S. MCEWEN

THE ALLOSTATIC LOAD MODEL 578 Allostatic Load and Externalized Behaviors/Conduct
Stress: Historical Background 578 Disorder in Children 598
The Hypothalamic-Pituitary-Adrenal Axis 579 Genetic Inf luences on the Hypothalamic-Pituitary-Adrenal
Stress, Stressor, Stress Response, Eustress, and Distress 579 Axis: Results from Twin Studies 607
Allostasis versus Homeostasis 581 FUTURE DIRECTIONS 611
Allostatic Load: When Things Turn Bad 582 The Hormonal Milieu of the Mother in the Prenatal and
Conclusion 590 Postnatal Periods 611
EARLY ADVERSITY AND THE DEVELOPMENT Inf luences of Early Adversities on Brain Development 614
OF ALLOSTATIC LOAD 590 GENERAL CONCLUSION 615
The Subjective Nature of Reality: The Human REFERENCES 616
Information-Processing System 593

Stress is a popular topic these days. A week seldom passes ple who are extremely stressed by time pressure and others
without hearing or reading about stress and its deleterious who actually seek time pressure to perform adequately (so-
effects on health. Given this negative impact of stress on called procrastinators). This shows that stress is a highly in-
human health, many types of stress management therapies dividual experience that does not depend on a particular
have been put forward to decrease stress and thus promote event such as time pressure; rather, it depends on specific
health. However, there is a great paradox in the field of psychological determinants that trigger a stress response.
stress research, and it relates to the fact that the popular
definition of stress is very different from the scientific def-
THE ALLOSTATIC LOAD MODEL
inition of stress. This has left a multitude of people and ex-
perts talking about, and working on, very different aspects
The allostatic load model proposed by McEwen and Stellar
of the stress response.
(1993) refers to the wear and tear that the body experiences
In popular terms, stress is mainly defined as time pres-
due to the repeated use of adaptive responses to stress, as
sure. We feel stressed when we do not have the time to per-
well as the inefficient turning on or shutting off of these re-
form the tasks we want to perform. This time pressure
sponses. Allostatic load refers to the cost the body pays for
usually triggers a set of physiological reactions (see discus-
this adaptation, when this adaptation needs to be main-
sion) that give us the indication that we are stressed. Al-
tained for long periods of time.
though this definition is certainly accurate in terms of one
component of the stress response, it is important to acknowl-
Stress: Historical Background
edge that in scientific terms, stress is not equivalent to time
pressure. If this were true, every individual would feel Prior to becoming part of our day-to-day conversations, the
stressed when pressured by time. However, we all know peo- term “stress” was used by engineers to explain forces that

578

can put strain on a structure. For example, one could place
strain on a piece of metal in such a way that it would break
like glass when it reached its stress level. In 1936, Hans
Selye (reproduced in Selye, 1998) borrowed the term from
the field of engineering and talked about stress as being a
nonspecific phenomenon representing the intersection of
symptoms produced by a wide variety of noxious agents.
For many years, Selye tested various conditions (e.g., fast-
ing, extreme cold, operative injuries, and drug administra-
tion) that would produce morphological changes in the
body that were representative of a stress response, such as
enlargement of the adrenal gland, atrophy of the thymus,
and gastric ulceration. Selye’s view of the concept of stress
was that the determinants of the stress response are non-
specific; that is, many unspecific conditions can put strain
on the organism and lead to disease, the same way that
many unspecific conditions can put strain on a piece of
metal and break it like glass.
Not all researchers agreed with Selye’s model, particu-
larly with the notion that the determinants of the stress re-
sponse are nonspecific. The reason for this was simple.
Selye spent his entire career working on physical stressors
(e.g., heat, cold, and pain), but we all know that some of the
worst stressors we encounter in life are psychological in na-
ture and are induced by our interpretation of events. For
this reason, a psychologist named John Mason (1968) spent
many years measuring stress hormone levels in humans
subjected to various conditions that he thought would be
stressful; he intended to describe the psychological charac-
teristics that would make any condition stressful to anyone
exposed to it. This work was made possible in the early
1960s due to the development of new technology that al-
lowed scientists to measure levels of hormones that are re-
leased during reactivity to stress. The release of stress
hormones is made possible through activation of a neuroen-
docrine axis named the hypothalamic-pituitary-adrenal
(HPA) axis.
The Hypothalamic-Pituitary-Adrenal Axis
When a situation is interpreted as being stressful, it trig-
gers the activation of the HPA axis, whereby neurons in the
hypothalamus, a brain structure often termed the “master
gland,” releases corticotropin-releasing hormone (CRH).
The release of CRH triggers the subsequent secretion and
release of another hormone, adrenocorticotropin (ACTH),
from the pituitary gland, also located in the brain. When
ACTH is secreted by the pituitary gland, it travels in the
blood and reaches the adrenal glands, which are located
above the kidneys, and triggers secretion of the so-called
The Allostatic Load Model 579
stress hormones. There are two main stress hormones, the
glucocorticoids (corticosterone in animals and cortisol in
humans) and the catecholamines (epinephrine and norepi-
nephrine). In humans, cortisol secretion shows pronounced
circadian rhythmicity, where concentrations are at their
highest in the morning (the circadian peak), progressively
decline from late afternoon to early nocturnal periods (the
circadian trough), and show abrupt elevations after the
first few hours of sleep. The acute secretion of glucocorti-
coids and catecholamines in response to a stressor consti-
tutes the primary mediators in the chain of hormonal
events triggered in response to stress. When these two hor-
mones are secreted in response to stress, they act on the
body to give rise to the fight-or-flight response, whereby
one would, for instance, experience an increase in heart
rate and blood pressure.
By summarizing the results of studies measuring the cir-
culating levels of these hormones before and after individ-
uals were exposed to various jobs or situations that were
deemed to be stressful (e.g., air-traffic controllers and
parachute jumping), Mason (1968) was able to describe
three main psychological determinants that would induce a
stress response in any individual exposed to them. Using
this methodology, he showed that for a situation to induce a
stress response, it has to be interpreted as being novel
and/or unpredictable, and/or the individual must have the
feeling that he or she does not have control over the situa-
tion. Although this work led to a general debate between
Selye (1975a) and Mason, further studies confirmed that
the determinants of the stress response are highly specific
and, therefore, potentially predictable and measurable.
Stress, Stressor, Stress Response, Eustress,
and Distress
From this short historical background, it is becoming clear
that various definitions have been given to stress. In the
past few years, a growing number of scientists started to
feel the need to clarify these concepts to increase our un-
derstanding of the effects of stress on human health. Based
on recent reviews, McEwen and Wingfield (2003) proposed
a clarification of these different concepts of stress that we
use in this review. Thus, we define stress as a threat, real or
implied, to homeostasis. In this sense, stress can be ab-
solute (a real threat induced by an earthquake in a town,
leading to a significant stress response in every person fac-
ing this threat), or it can be relative (an implied threat in-
duced by the interpretation of a situation as being novel
and/or unpredictable and/or uncontrollable, for example, a
public speaking task).
580 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
Absolute versus Relative Stressors
Absolute stressors serve adaptive purposes and are those
events or situations that will necessarily lead to a stress re-
sponse in the majority (if not the totality) of individuals
when they are first confronted with it. Being in or witness-
ing an accident, confronting a dangerous animal, being sub-
mitted to extreme cold or heat are all examples of absolute
stressors. These extreme and particular situations constitute
absolute stressors in that, due to their aversive nature, a
stress response has to be elicited for one’s survival and/or
well-being. In Western societies, absolute stressors are rare
but are nonetheless those that elicit the greatest physiologi-
cal response. Conversely, relative stressors are those events
or situations that will elicit a stress response only in a cer-
tain proportion of individuals. Moreover, this response may
be mild or strong. For example, having to unexpectedly de-
liver a speech that will be videotaped may be very stressful
for one individual and not at all for another. Large interindi-
vidual variations in the stress response to psychological
challenges have been frequently reported (Hellhammer,
Buchtal, Gutberlet, & Kirschbaum, 1997; Kirschbaum &
Hellhammer, 1989; Kirschbaum, Klauer, Filipp, & Hellham-
mer, 1995; Kirschbaum, Kudielka, Gaab, Schommer, &
Hellhammer, 1999; Kirschbaum, Prussner, et al., 1995;
Kudielka, Buske-Kirschbaum, Hellhammer, & Kirschbaum,
2004; Kudielka, Schommer, Hellhammer, & Kirschbaum,
2004; Lupien et al., 1997; M. Pruessner, Hellhammer,
Pruessner, & Lupien, 2003; Rohleder, Wolf, & Kirschbaum,
2003; Roy, Steptoe, & Kirschbaum, 1998). As discussed in
section II of this chapter, these individual differences in re-
sponse to relative stressors may be due to differences in past
experiences, learning, or genetic or cognitive processes.
However, most of the relative stressors that lead to large in-
terindividual variations are those stressors that imply a cog-
nitive and/or psychosocial component (Dickerson &
Kemeny, 2002). It may be argued that absolute stressors are
closely linked to physiological systems due to their life- or
self-threatening nature. On the contrary, relative stressors,
because they are milder or because they necessitate a cogni-
tive interpretation to elicit a response, will not necessarily
lead to a physiological response, and the presence or absence
of a physiological response will depend on the outcome of
the cognitive analysis.
Eustress versus Distress
Situations can be interpreted as being positive, leading to
eustress (good stress), or as being negative, leading to dis-
tress ( bad stress). The nature (eustress versus distress) of
the stress response elicited by these situations relates
more to the cognitive interpretation given to the situation
(as being positive or negative to the individual) than to the
physical consequence of it. To date, very few studies have
been performed to assess the body’s different responses
to eustress or distress. However, a study performed in
1989 by Berk and collaborators assessed the hormonal re-
sponse to a mirthful laughter experience in 10 healthy
male subjects. In this study, half of the participants
viewed a 60-minute humorous video and the other half
did not. Measures of cortisol, 3,4-dihydrophenylacetic
acid (dopac, the major serum neuronal catabolite of the
neurotransmitter dopamine), epinephrine, and norepi-
nephrine were assessed before and after exposure to the
experimental or control conditions. The results showed
that cortisol and dopac in the experimental group de-
creased more rapidly from baseline than in the control
group, whereas epinephrine levels in the experimental
group were significantly lower than in the control group at
all time points. Although the authors stated that these bio-
chemical changes have implications for the reversal of the
neuroendocrine and classical stress hormone response, it
has to be noted that the study was performed with a very
small sample of participants (5 in each group), and the
cortisol changes in response to the funny movie were not
compared to the cortisol changes after exposure to a sad
or aggressive movie. Consequently, it is not clear at this
time whether feelings of eustress or distress lead to dif-
ferent hormonal responses in humans.
Stressor versus Stress Response
The stressor is the event itself, such as the earthquake in
the case of the absolute stress or the public speaking task in
the case of the relative stress. The stress response is the
body’s reaction to the event (Selye, 1975b, 1998) and can
be measured by monitoring levels of cortisol and ACTH in
blood or cortisol in saliva or urine. Activity within the
sympathetic nervous system is measurable as levels of cate-
cholamines in blood, urine, or saliva or by monitoring heart
rate and blood pressure. Although the subjective experi-
ence of stress does not always correlate with the output of
the physiological mediators of stress (Kirschbaum et al.,
1999), the measurement of the body’s physiological re-
sponses to environmental challenges (real or implied)
nonetheless constitutes the primary means of connecting
experience with resilience or the risk of disease.
Acute versus Chronic Stress
Activation of the stress response in the face of a threat
(real or implied) is primordial for the survival of
the species. This acute stress response, which has been

called the fight-or-flight response, allows the individual to
mobilize the energy required to deal with threat. However,
chronic exposure to these threats can have detrimental ef-
fects on the body. Although a wealth of data has been gath-
ered on the effects of chronic stress on the body, almost no
model has been offered to explain, predict, and measure
the impact of chronic stress on the body. The main reason
for this is the fact that no model has proposed a clear dis-
tinction between the positive impact of an acute response
to stress and the negative impact of a chronic activation of
the stress systems. Moreover, in many cases, a stressor is
thought to refer to any situation that challenges the body’s
homeostasis and consequently is seen as being negative.
However, in recent years, a new model has been developed
to disentangle these different concepts and allow for a
clearer description of the positive and negative effects of
acute and chronic stress on the organism. This is the allo-
static load model (McEwen & Stellar, 1993), but to under-
stand what allostatic load is, one has to first understand the
notion of allostasis and how it differs from the notion of
homeostasis.
Allostasis versus Homeostasis
In 1929, Cannon introduced the term “ homeostasis” to
refer to the operation of coordinated physiological
processes that maintain most of the steady states of the
organism. Consequently, homeostasis is the stability of
physiological systems that maintain life, such as pH, body
temperature, glucose levels, and oxygen tension. These
physiological systems are truly essential for life and are
therefore maintained within an optimal range. The daily
routines of animals and humans include nutritional inputs
to maintain normal activities and to anticipate additional
requirements (such as breeding, acclimating to environ-
mental changes) during the day-night cycle and the sea-
sons. These homeostatic mechanisms allow the individual
to maintain physiological and behavioral stability despite
fluctuating environmental conditions.
However, life is not always stable, and superimposed
on these predictable events are facultative physiological
and behavioral responses to unpredictable events that
have the potential to be stressors. To respond to these un-
predictable events, the system requires extra energy from
endogenous stores of fat, glycogen, and protein. Conse-
quently, to survive, an organism must be able to maintain
such emergency responses. The capacity to maintain
these emergency responses has been called “allostasis”
(Sterling & Eyer, 1988), which implies the process of
adaptation (McEwen & Stellar, 1993). Allostasis, mean-
The Allostatic Load Model 581
ing literally “maintaining stability through change,” de-
scribes the process of adaptation to challenge. It was in-
troduced by Sterling and Eyer in 1988 to describe how the
cardiovascular system adjusts to resting and active states
of the body. This notion was generalized to other physio-
logical mediators, such as the secretion of cortisol and
catecholamines (McEwen, 1998a, 1998b; McEwen & See-
man, 1999; McEwen & Stellar, 1993).
Allostasis is positive and necessary to life. It is different
from homeostasis in that it supports homeostasis; that is, it
supports those physiological parameters essential for life, as
environments and/or life history stages change. Indeed,
homeostasis keeps “set-points” and various boundaries of
control (such as pH), whereas allostasis allows for a modifi-
cation of these set-points in order to face challenges. Conse-
quently, homeostasis involves systems that are essential for
life, and allostasis maintains these systems in balance as en-
vironment and life history stage change (McEwen & Wing-
field, 2003).
For each system of the body, allostasis allows for short-
term adaptive actions of the organism in response to envi-
ronmental change. As presented in Table 14.1, for the
cardiovascular system, one good example of allostasis is
the role of catecholamines in promoting adaptation by ad-
justing heart rate and blood pressure to various conditions
such as sleeping, waking, and physical exertion (Sterling &
Eyer, 1988). For the metabolic system, one example of
allostasis is the role of glucocorticoids at enhancing
food intake and facilitating the replenishment of energy re-
serves after an environmental challenge (Beauman, 2000;
Kuenzel, Beck, & Teruyama, 1999). For the brain, a good
example of allostasis is the involvement of both glucocorti-
coids and catecholamines in promoting memory for emo-
tionally meaningful events related to the environmental
changes (Cahill, Prins, Weber, & McGaugh, 1994; Maheu,
Joober, Beaulieu, & Lupien, 2004; Maheu & Lupien, 2003;
Roozendaal, 2000, 2003; Roozendaal, Hahn, Nathan, de
Quervain, & McGaugh, 2004; van Stegeren, Everaerd,
Cahill, McGaugh, & Gooren, 1998). For the immune sys-
tem, an example of allostasis is the role of glucocorticoids
and catecholamines in promoting trafficking of immune
cells to organs and tissues where they are needed to fight
an infection or other challenges (Dhabhar & McEwen,
1999). All these body responses go above homeostatic
functions and serve to maintain the stability of the various
systems of the body in response to environmental chal-
lenges. It is because allostasis allows for a change in the
set-points of these various physiological systems that
homeostasis is kept, and the body can respond adequately
to environmental changes.
582 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective

TABLE 14.1 Examples of Allostasis and Allostatic Load Processes, along with the Primary Stress Mediators Involved, for the
Cardiovascular, Metabolic, Immune, and Brain Systems

System Primary Stress Mediator Involved Allostasis Allostatic Load

Cardiovascular Catecholamines Act by promoting adaptation by adjusting
heart rate (HR) and blood pressure (BP)
to sleeping, waking, and physical exertion.
Metabolic Glucocorticoids Enhance food intake and facilitate
replenishment of energy reserves.
Immune Glucocorticoids and Catecholamines Promote trafficking (movement) of
immune cells to organs and tissues where
they are needed to fight infections or other
challenges and modulate the expression of
the hormones of the immune system, i.e.,
the cytokines and the chemokines.
Brain Glucocorticoids and Catecholamines Promote retention of memories for
emotionally charged events, both positive
and negative.
Repeated surges of BP accelerates
atherosclerosis and synergizes with
metabolic hormones to produce Type II
diabetes.
Repeated HPA activity leads to insulin
resistance, accelerating toward
progression of Type II diabetes, including
abdominal obesity, atherosclerosis, and
hypertension.
Chronic overactivity of these mediators
leads to immunosuppressive effects.
Overactivity of these mediators lead to
cognitive dysfunction, reduces neuronal
excitability, induces neuronal atrophy, and
in extreme cases, causes death of brain cells.

Allostatic Load: When Things Turn Bad
In 1993, McEwen and Stellar proposed the term “allostatic
load” to refer to the wear and tear that the body experiences
due to the repeated use of allostatic responses as well as the
inefficient turning on or shutting off of these responses. Al-
lostatic load refers to the cost the body pays for this adapta-
tion, when this adaptation needs to be maintained for long
periods of time. From the standpoint of survival and health
of the individual, the most important feature of the primary
stress mediators associated with allostasis is that they have
protective effects in the short run. However, they can have
damaging effects at longer time intervals if there are many
adverse life events or if the secretion of hormones is dysreg-
ulated due to sustained stress responses. When this happens,
it leads to allostatic load. As presented in Figure 14.1,
McEwen and Stellar’s model describes the operating factors
and the general sequence of events that occurs under condi-
tions of acute and chronic stress (for reviews of the concept,
see McEwen, 1998a, 1998b; McEwen & Seeman, 1999;
McEwen & Stellar, 1993; McEwen & Wingfield, 2003; See-
man, McEwen, Rowe, & Singer, 2001). The model comprises
a behavioral side, on which the individual interprets and re-
acts to a challenge, and a biological side, on which the body
reacts to the perceived stress. The model thus comprises
both a top-down processing side (interpretation of a situa-
tion as being stressful, leading to activation of the various
stress systems) and a bottom-up side (the effects of the
acute and/or prolonged activation of these systems on the
body and the brain).
Top-Down Processing and Allostasis
The first factor in McEwen and Stellar’s (1993) model is the
reaction of the individual to physical and psychological stim-
uli. As presented in Figure 14.1, this reaction is in part de-
termined by the social context and the social status of the
individual. Second, the stimulus will have an effect on the
individual’s information-processing system (the “proces-
sor ”). The response of the processor will be determined by
genetic makeup, stage of biological development, gender,
past learning, and social history. If the stimulus is perceived
as a threat and the source of the threat is unknown, the indi-
vidual will become highly vigilant and try to determine the
real nature (threat versus nonthreat) of the stimulus. If the
stimulus is perceived as a threat and its source is known, the
individual will try to find a coping response to the threat. If
no response is available, helplessness or hopelessness may
appear, with its altered physiologic responses. If a response
is available, the outcome of it will depend on the cost of that
response. If a low-cost response is appropriate, no stress re-
sponse will be initiated. If a high-cost response is needed, it
may necessitate the appearance of aggression or sensation-
seeking or risk-taking behaviors. However, the available re-
sponse can also be thwarted, which will eventually lead to
displaced frustration or aggression. So, perceptions of threat
and choice of response are central aspects of the assessment
 The Allostatic Load Model 583

Social context Physical and which will help trigger a stress response allowing the indi-
Social status Stimulus psychological vidual to deal with the threat. What is important to under-
challenges
stand here is that the same mediators (glucocorticoids and
Genetic predisposition Learning, individual, catecholamines) that are protective and adaptive in the short
Developmental stage Processor and social history run can have extremely damaging consequences if they are
Gender
overproduced and/or are dysregulated for a longer period of
Threat
time (McEwen, 1998a), leading to biphasic actions of the
No Threat
primary stress mediators.
The long-term cost to the body from allostatic load may
Source Known Source Unknown
be subdivided into at least four subtypes (McEwen, 1998a),
as summarized in Figure 14.1. The first type is simply too
Response Unavailable Response Available much stress in the form of repeated, novel events that cause
repeated elevations of stress mediators. For example, the
Low Cost High Cost amount and frequency of economic hardship predicts de-
Thwarted
cline of physical and mental functioning as well as mortal-
Response ity (Adler et al., 1994). A second type of allostatic load
involves a failure to habituate or adapt to the multiple oc-
currences of the same stressor. This leads to the overexpo-
Activation of Primary Stress Mediators
(cortisol, epinephrine, norepinephrine, DHEA)
sure to stress mediators because the body fails to dampen
or eliminate the hormonal stress response to a repeated
Response

event. For example, when confronted with repeated public

Allostasis

speaking challenges, most individuals habituated their cor-

tisol response, but a few individuals continued to show cor-
Stress Recovery
tisol response (Kirschbaum, Prussner, et al., 1995). A third
Primary Mediators and Effects

type of allostatic load involves the failure to shut off either

Primary Effects
Long-Term Activation of

the hormonal stress response or the normal trough of the

(cellular events regulated by primary mediators)
diurnal cortisol pattern. Examples of this include blood
pressure elevations in work-related stress (Gerin, Litt,
Deich, & Pickering, 1996; Kunz-Ebrecht, Kirschbaum, &
Repeated Lack of Prolonged Inadequate
Hits Adaptation Response Response Steptoe, 2004; Lundberg, 1996; Ming et al., 2004; Picker-
ing, 1996a, 1996b; Pickering et al., 1996; Schwartz, Picker-
Secondary Outcomes
ing, & Landsbergis, 1996; Steptoe, Siegrist, Kirschbaum,
(waist-hip ratio, blood pressure, cholesterol, glucose) & Marmot, 2004; Steptoe & Willemsen, 2004), sleep dep-
rivation leading to elevated evening cortisol and hyper-
Allostatic

(insulin, immune capacity, glucose tolerance) glycemia within 5 days (Leproult, Copinschi, Buxton, &
Load

Van Cauter, 1997; Van Cauter, Polonsky, & Scheen, 1997),

Tertiary Outcomes and depressive illness leading to chronically elevated corti-
(cardiovascular disease, severe cognitive decline, sol and loss of bone mineral mass (Coelho, Silva, Maia,
diabetes, hypertension, cancer) Prata, & Barros, 1999; Michelson et al., 1996; Robbins,
Hirsch, Whitmer, Cauley, & Harris, 2001; Wong et al.,
Figure 14.1 Schematic representation of the Allostatic Load
model. 2005). The fourth type of allostatic load involves an inade-
quate hormonal stress response which allows other sys-
of risk and making choices leading to health-damaging or tems, such as the inflammatory cytokines, to become
health-promoting behaviors. overactive (Chrousos & Elenkov, 2000; Elenkov, Chrousos,
& Wilder, 2000). The Lewis rat is an example of an animal
Bottom-Up Effects and Allostatic Load strain in which increased susceptibility to inflammatory
When a given situation is perceived as stressful or threaten- and autoimmune disturbances is related to inadequate lev-
ing, there will be activation of the primary stress mediators els of cortisol (for a review, see Fournie et al., 2001). Next,
(glucocorticoids, catecholamines, dehydroepiandrosterone we give an example of allostasis turning into allostatic load
[DHEA]; a complete description of these mediators follows), for the primary stress mediator glucocorticoids.
584 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
Glucocorticoids and Allostatic Load: An Example.
The traditional role of glucocorticoids is to promote con-
version of protein and lipids to usable carbohydrates. In the
short run, this is a positive aspect of this stress mediator
as glucocorticoids will serve to replenish energy reserves
after a period of activity such as running away from a
house on fire. The same glucocorticoid will also act on the
brain during this period to increase appetite for food (to re-
plenish energy reserves) and to increase locomotor activity
and food-seeking behavior (to increase energy expendi-
tures; Leibowitz & Hoebel, 1997; Tang, Akabayashi, Man-
itiu, & Leibowitz, 1997). These effects of glucocorticoids
are very beneficial when we have to run as fast as we can
from a house on fire and when we have to replenish our en-
ergy after this intense running to maintain our daily activi-
ties. However, these effects can be detrimental when the
stress response is triggered chronically by an absolute (e.g.,
always having to run away from a predator) or relative (e.g.,
a low sense of control at work) stressor.
There is an important point to make with regard to the
impact of relative stressors on allostasis and allostatic
load. The primary stress mediator ( here, glucocorticoids)
does not distinguish between a real (a house on fire) and an
implied ( low sense of control) threat; consequently, its ac-
tivation will occur at each occurrence of the stressor (real
or implied), leading to long-term secretion of glucocorti-
coids. Moreover, the action of glucocorticoids will be the
same, that is, action on the brain to increase appetite for
food (replenishment of energy reserves) and increase loco-
motor activity (energy expenditures). Given that, in the
case of a relative stressor, the stress response has been trig-
gered by a psychological situation rather than a real threat
to survival (absolute stressor), the energy expenditure is
less, but the glucocorticoids have been secreted at the same
levels, activating the brain in the same way to increase food
intake, with a preference for carbohydrates. Given that in
Western societies, food is easily available and does not ne-
cessitate a lot of food-seeking behaviors, the energy expen-
diture resulting from food-seeking behavior is low. In the
long run, inactivity and lack of energy expenditure, along
with increased secretion of glucocorticoids, creates a situ-
ation where chronically elevated glucocorticoids can im-
pede the action of insulin to promote glucose uptake. One
of the results of this interaction is that insulin levels in-
crease and, together, high insulin and glucocorticoids con-
centrations promote the deposition of body fat. This
combination of hormones will also promote the formation
of atherosclerotic plaques in coronary arteries, increasing
the risk for coronary diseases (Brindley & Rolland, 1989).
It is when a dysregulation of other hormones occurs in re-
sponse to the long-term secretion of the primary stress me-
diators that allostatic load appears. Other examples of
allostatic load are depicted in Table 14.1 for the cardiovas-
cular, metabolic, immune, and brain systems.
When Top-Down Processing Meets Bottom-Up Effects
As we have summarized above, once a situation has been
interpreted as being threatening, a stress response will be
activated, which might lead to allostatic load. What is in-
teresting to take into account in this context is that some of
the hormones secreted during the stress response will ac-
cess the brain and will modify the way that further upcom-
ing information is processed.
Allostatic Load and the Brain. As we noted earlier,
one of the most important parts of the allostatic load model
is the cognitive processor, which acts by deciding whether
a situation constitutes a threat or not. Once this processing
has been done, there will be activation (threat) or not (non-
threat) of the primary stress mediators.
It is important to note here that these primary mediators
(particularly glucocorticoids and catecholamines) have
been shown to have important effects on the brain, leading
to changes in cognitive processing. Here again, a process of
allostasis and allostatic load has been observed with regard
to the effects of the primary stress mediators on the brain.
Allostatic Effects on the Brain. Given the lipophilic
properties of glucocorticoids, these adrenal hormones can
easily cross the blood-brain barrier and enter the brain,
where they can influence brain function and behavior by
way of binding to different receptor types. Three of the
most important brain areas containing glucocorticoid re-
ceptors are the hippocampus, amygdala, and frontal lobes,
which are brain structures known to be involved in learning
and memory (for reviews, see Lupien & Lepage, 2001;
Lupien & McEwen, 1997). Although epinephrine does not
readily access the brain due to absence of lipophilic prop-
erties, it can still act on the brain through its action on the
sensory vagus outside of the blood-brain barrier, with in-
formation transmitted into the brain via the nucleus of the
solitary tract (for a review, see Roozendaal, 2000). The
most important brain area containing adrenergic receptors
is the amygdala, which has been shown to play an impor-
tant role in fear processing (for a recent review, see
LeDoux, 2003) and memory for emotionally relevant infor-
mation (for a recent review, see McGaugh, 2000).

Because of their actions on brain structures known to
be involved in fear detection and memory for emotionally
relevant information, the stress mediators enhance the for-
mation of the so-called flashbulb memories of events asso-
ciated with strong emotions, including fear but also
positive emotions. This process involves the amygdala,
and the pathway for encoding these memories involves the
interaction between neurotransmitters in the amygdala
and in related brain areas such as the hippocampus along
with circulating stress hormones of the adrenal cortex and
adrenal medulla (McGaugh, 2000; Roozendaal, Hahn,
et al., 2004; Roozendaal, McReynolds, & McGaugh, 2004;
van Stegeren et al., 1998). The importance of these stress
mediators on memory for emotionally relevant informa-
tion has been recently confirmed by studies in which
blockade of either glucocorticoid (Maheu et al., 2004) or
norepinephrine (Cahill et al., 1994) activity impaired the
recall of emotionally relevant information. Consequently,
secretion of these primary stress mediators is necessary
for the adequate encoding of emotionally relevant infor-
mation. This enhancement of memory for stimuli inducing
stressful and/or emotional responses may be essential for
a species’ survival.
At the same time as the brain encodes information and
controls the behavioral responses, it is also changed struc-
turally and chemically by those experiences. Although for a
long time it was thought that the brain of adult mammals does
not generate new nerve cells, more recent evidence showed
that neurons are born in the adult mammalian brain (Altman
& Das, 1965). Interestingly, in the adult brain, the generation
of new neurons (called neurogenesis) occurs in two regions.
The first region is the subventricular zone in the wall of the
lateral ventricle, where new interneurons are generated for
the olfactory bulb; the second region is the subgranular zone
of the dentate gyrus of the hippocampus, which gives rise
to the granule cells. Moreover, recent evidence shows that
adult neurogenesis in the dentate gyrus of the hippocampus
is a feature of all mammalian species, occurring in rats,
mice, tree shrews, marmosets, macaques, and humans (H. A.
Cameron, Woolley, McEwen, & Gould, 1993; Eriksson et al.,
1998; Gould, McEwen, Tanapat, Galea, & Fuchs, 1997;
Gould et al., 1999; Gould, Tanapat, McEwen, Flugge, &
Fuchs, 1998; Kempermann, Kuhn, & Gage, 1997). Although
the functional significance of hippocampal neurogenesis has
been questioned in the past, a study published in the March
2001 issue of Nature reported that neurogenesis in the adult
is involved in the formation of trace memories, suggesting
that the new neurons actually contribute to the function of
the adult brain (Shors et al., 2001).
The Allostatic Load Model 585
Gould and collaborators (1999) reported that training on
a task that requires the hippocampal formation results in an
increase in the number of adult-generated granule cells.
Of particular importance, these authors showed that in un-
trained adult laboratory animals, the majority of generated
cells degenerate within 2 weeks of production, whereas
training on hippocampal-dependent tasks rescued a signifi-
cant proportion of these cells. In line with experiments
showing experience-dependent changes in hippocampal
volumes, studies performed in adult neurogenesis show that
learning can enhance the number of granule neurons. Also,
comparative studies of different species show that hip-
pocampal volume is increased in mammalian and avian
species that depend critically on spatial memory for sur-
vival. Examples of such critical memory skills involve
home-range navigation, migration, brood parasitism, and
memory-based cache recovery in birds that hide food
(Suzuki & Clayton, 2000). This association between per-
formance of spatial tasks and hippocampal size could
be explained in terms of the impact of environmental de-
mands on hippocampal volume, rather than the converse.
For example, Clayton and collaborators (Clayton & Krebs,
1994; Gerlai & Clayton, 1999) reported that the hippocam-
pus of titmice and chickadees increases in volume in asso-
ciation with the experience of storing and recovering food
caches. This result shows that in animals, there can be an
experience-dependent hippocampal growth that occurs at
a relatively late stage in development. Similar results of
experience-based changes in hippocampal volumes were
recently reported by Maguire and collaborators (2000) in
humans. These authors tested the hypothesis that the abil-
ity of London taxi cab drivers to navigate to a specific des-
tination correlates with hippocampal volume. They showed
that compared to age-matched controls, the taxi drivers had
larger posterior hippocampi. Although these results surely
do not confirm that the experience of driving a taxi in the
complex streets of London has a significant effect on hip-
pocampal volumes, they nonetheless raise the intriguing
possibility of hippocampal plasticity in response to envi-
ronmental demands.
Allostatic Load Effects on the Brain. Although
short-term responses of the brain to novel and potentially
threatening situations may be adaptive and result in new
learning and acquired behavioral strategies for coping,
as may be the case for certain types of fear-related memo-
ries, repeated stress can cause both cognitive impairments
and structural changes in the hippocampus. Each of these
processes may be occurring somewhat independently of
586 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
each other and contribute in various degrees to different
pathophysiological situations involving traumatic stress,
depression, or aging.
The cognitive effects of long-term elevations of gluco-
corticoids in human populations have been studied in disor-
ders affecting glucocorticoid levels and using exogenous
administration of the synthetic compound to healthy sub-
jects (for a review, see Lupien & Lepage, 2001). Mental
disturbances mimicking mild dementia (such as decre-
ments in simple and complex attentional tasks, verbal and
visual memory, encoding, storage, and retrieval) have been
described in depressed patients with hypercortisolism (R.
M. Cohen, Weingartner, Smallberg, Pickar, & Murphy,
1982; Rubinow, Post, Savard, & Gold, 1984; Vythilingam
et al., 2004; Weingartner, Cohen, Murphy, Martello, &
Gerdt, 1981; Wolkowitz et al., 1988; Wolkowitz et al.,
1990) and in steroid psychosis following glucocorticoid
treatment (Hall, Popkin, Stickney, & Gardner, 1979; Ling,
Perry, & Tsuang, 1981; Varney, Alexander, & MacIndoe,
1984; Wolkowitz, Reus, Canick, Levin, & Lupien, 1997).
Similar cognitive deficits are also reported in patients suf-
fering from Cushing’s disease (O. G. Cameron, Starkman,
& Schteingart, 1995; Starkman, Gebarski, Berent, &
Schteingart, 1992; Starkman, Giordani, Berent, Schork, &
Schteingart, 2001; Starkman et al., 1999; Starkman, Gior-
dani, Gebarski, & Schteingart, 2003). During human aging,
a significant proportion of elderly individuals present an
endogenous increase of glucocorticoid levels (Lupien et al.,
1996), and this increase has been related to impaired mem-
ory performance (Lupien et al., 1994).
Although an allostatic process has been shown to lead
to positive structural changes of the hippocampus, it is im-
portant to note that an allostatic load process has also
been shown to have significant detrimental effects on this
brain structure. For example, treatment of adult rats with
corticosterone decreases the proliferation of granule cell
precursors (H. A. Cameron & Gould, 1994), and removal
of adrenal steroids stimulated the generation of new gran-
ule neurons (H. A. Cameron & McKay, 1999). Given the
suppressive actions of glucocorticoids on hippocampal
neurogenesis, stressful experiences have been suggested to
inhibit cell proliferation in adulthood, a hypothesis that
has been demonstrated. Long-term stressful experience
decreases the number of adult-generated neurons in the
dentate gyrus in various species, including the rat (Heale,
Vanderwolf, & Kavaliers, 1994; Sgoifo, de Boer, Haller, &
Koolhaas, 1996), tree shrew (Gould et al., 1997), and mar-
moset (Gould et al., 1998). In a similar vein, repeated
stress produces prolonged suppression of cell proliferation
in the dentate gyrus of the adult tree shrew (Fuchs, Uno,
& Flugge, 1995). Stress-induced decreases in dentate
gyrus cell proliferation could also contribute, in line with
atrophy of the pyramidal cells of the hippocampus, to
changes in hippocampal volumes observed after chronic
exposure to stress.
Smaller hippocampal volumes associated with chronic
elevations of glucocorticoids have also been reported in hu-
mans. Over the past 2 decades, many studies revealed the
presence of smaller hippocampal volumes in various psy-
chiatric disorders, such as depression (Krishnan et al.,
1991; Sheline, 1996; Sheline, Gado, & Kraemer, 2003; She-
line, Sanghavi, Mintun, & Gado, 1999; Sheline, Wang,
Gado, Csernansky, & Vannier, 1996; Vythilingam et al.,
2004), Posttraumatic Stress Disorder (Bremner, 2002,
2003; Vythilingam et al., 2002), and Schizophrenia (Heck-
ers, 2001; Nelson, Saykin, Flashman, & Riordan, 1998), all
of which involve glucocorticoid-level dysregulations. Hip-
pocampal atrophy associated with chronic exposure to high
levels of glucocorticoids is also reported in patients with
Cushing’s disease (Starkman et al., 1992; Starkman et al.,
1999) and elderly individuals (Lupien et al., 1998). A re-
cent study of Cushing’s patients revealed that surgical
treatment of hypercortisolism in these patients leads to a
reversal of the glucocorticoid-induced hippocampal atro-
phy reported to occur in this population, with an average
volume increase of 3.2% and variations up to 10% in some
patients (Starkman et al., 1999). This is a significant find-
ing as it implies the possibility of functional reorganization
of the hippocampus once the allostatic load process has
been taken away. Reversibility and/or preventability of
such atrophy is a major topic for future research, as is the
implication of such treatment for cognitive function.
Chronology of the Allostatic Load Process. As we
have stated in previous sections, the activation of the pri-
mary stress mediators represents an allostatic process
whereby an adaptive response to an environmental threat is
organized. However, after repeated exposure to various sit-
uations that lead to activation of these stress mediators
(either through repetitive hits, failure to habituate, pro-
longed response, or inadequate response), allostatic load
will develop. Consequently, there exists a chronology of
hormonal and cellular events in the development of allosta-
tic load that can allow for a measure of the level of allosta-
tic load in any given individual. The chain of events in the
allostatic load process begins with the allostatic activation
of primary mediators, with the resulting primary effects.
After prolonged allostatic attempts at adaptation, other
 The Allostatic Load Model 587

hormonal and cellular processes will become dysregulated,

TABLE 14.2 Various Stages of Allostatic Load and the
leading to secondary and tertiary outcomes. We summarize Physiological and Clinical Markers Used to Assess the
these next. Degree of Allostatic Load
Stages of Allostatic Load Physiological and Clinical Markers
Primary Mediators of Allostatic Load. The primary Primary mediators Glucocorticoids
mediators of allostatic load are those chemical messengers DHEA
that are released as part of allostasis (see Table 14.2). At Adrenaline
present, there are four primary mediators included in the Noradrenaline
assessment of allostatic load: cortisol, epinephrine, norepi- Cytokines
nephrine (the catecholamines), and DHEA. These chemical Primary effects Cellular events (enzymes, receptors, ion
messengers are primary mediators because they have wide- channels, structural proteins) that are reg-
ulated by the primary mediators as part of
spread influence throughout the body and are very useful
allostasis (not well studied).
(when measured correctly) at predicting a variety of sec-
Secondary outcomes Ref lect the cumulative outcomes of the
ondary and tertiary outcomes. primary effects and the outcomes of more
As summarized earlier, cortisol (the most important glu- than one primary mediator.
cocorticoid in humans) has wide-ranging effects through- Waist-hip ratio
out the body. Receptors for glucocorticoids are present in Blood pressure (systolic and diastolic)
virtually every tissue and organ in the body and mediate ef- Heart rate
fects ranging from the induction of liver enzymes involved Glycosylated hemoglobin
HDL (High Density Lipoprotein)
in energy metabolism to regulating the trafficking of im-
Total cholesterol
mune cells and cytokine production to facilitating the for-
Glucose
mation of fear-related memories.
Insulin
DHEA is a functional antagonist of cortisol (May, Poor glucose tolerance
Holmes, Rogers, & Poth, 1990; Wright, Porter, Browne, & Nitric oxide
Svec, 1992) that may also have effects via other signaling Fibrinogen
pathways (Araneo & Daynes, 1995); generally, low DHEA Immune delayed-type hypersensitivity
is considered deleterious, as is chronically high cortisol Immunization challenge response
(Morales, Nolan, Nelson, & Yen, 1994). Blood level of Frequency and severity of common cold
DHEA, most of which is present in the sulfated form Mild cognitive decline unrelated to age
(DHEAS), peaks at approximately 20 years of age and de- Tertiary outcomes Actual diseases or disorders that are the
clines rapidly and markedly after age 25 (Orentreich, result of the allostatic load that are pre-
dicted from the extreme values of the sec-
Brind, Rizer, & Vogelman, 1984). The accumulation of ondary outcomes and of the primary
abdominal fat increases with aging, and abdominal obesity mediators.
increases the risk for development of insulin resistance, Cardiovascular disease
diabetes, and atherosclerosis (Cefalu et al., 1995). In Severe cognitive decline
rats, DHEA has protective effects against both the insulin Decreased physical capacity
resistance induced by a high-fat diet (Hansen, Han, Nolte, Cancer

Chen, & Holloszy, 1997) and the decrease in insulin
responsiveness that occurs with advancing age (Han,
Hansen, Chen, & Holloszy, 1998).
The catecholamines epinephrine and norepinephrine are
released by the adrenal medulla and sympathetic nervous
Note: It is important to note that there are other primary mediators that
may be included in the allostatic load model, but we have selected a
subset of these for clarity. These potential additional mediators are pre-
sented in italics and are not discussed in the text. Also, it is important
to underline that all these mediators operate as an interacting network
and not necessarily in a linear fashion, as the table might suggest.

system, respectively, and produce widespread effects

throughout the body, ranging from vasoconstriction and ac-
celeration of heart rate to trafficking of immune cells to
targets, as well as enhancement of fear-related memory for-
mation (Cahill et al., 1994). Adrenergic receptors are wide-
spread throughout the body, in blood vessels and target
organs such as the liver, pancreas, and brain, which is not
accessible to circulating catecholamines. However, cate-
cholamines signal the brain through the sensory vagus and
the nucleus of the solitary tract, as in learned fear.
Primary Effects of Allostatic Load. The primary ef-
fects of allostatic load have not been measured extensively,
but these include cellular events, the actions of enzymes,
588 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
receptors, ion channels, and/or structural proteins that are
induced genomically or phosphorylated via second messen-
ger systems that are regulated as part of allostasis by the
primary mediators (see Table 14.2).
For example, glucocorticoids regulate gene expression
via several pathways, involving interactions with DNA via
the glucocorticoid response elements and also via protein-
protein interactions with other transcriptional regulators
(Miner, Diamond, & Yamamoto, 1991). As noted earlier,
DHEA antagonizes glucocorticoid actions in a number of
systems. Catecholamines act via alpha and beta adrenergic
receptors, and beta receptors stimulate the formation of
the intracellular second messenger, cyclic AMP (cAMP),
which, in turn, regulates intracellular events via phospho-
rylation, including transcription regulators via the CREB
family of proteins (Siegel, Agranoff, Albers, Fisher, &
Uhler, 1999).
In some cases, the glucocorticoid and cAMP pathways
converge at the level of gene expression (e.g., see Yamada,
Duong, Scott, Wang, & Granner, 1999). Therefore, it is not
surprising that secondary outcomes (see later discussion)
are the result of more than one primary mediator. Conse-
quently, primary effects are organ- and tissue-specific, and
secondary outcomes reflect the integrated actions of the
primary effects.
Secondary Outcomes. The secondary outcomes are
the integrated processes that reflect the cumulative out-
comes of the primary effects in a tissue/organ-specific
manner in response to the primary mediators (see Table
14.2). Consequently, they often reflect the actions of more
than one primary mediator. Examples of secondary out-
comes are evident in waist-hip ratio (abdominal fat deposi-
tion), blood pressure elevation, glycosylated hemoglobin,
the ratio of cholesterol to HDL High Density Lipoproteins
(HDL), and HDL cholesterol. These are secondary out-
comes because they reflect the effects of sustained eleva-
tions in glucose and the insulin resistance that develop
as a result of elevated cortisol and elevated sympathetic
nervous system activity (primary mediators). Blood pres-
sure elevation is part of the pathophysiological pathway of
metabolic syndrome but is also a more primary indication
of the allostatic load that can lead to accelerated athero-
sclerosis as well as insulin resistance. Cholesterol and
HDL cholesterol are measures of metabolic imbalance in
relation to obesity and atherosclerosis and also reflect the
operation of the same primary mediators as well as other
metabolic hormones.
Another important secondary outcome is mild cognitive
decline without dementia; this secondary outcome relates to
the detrimental effects of long-term exposure to high
levels of glucocorticoids and catecholamines on cognitive
processing in humans (Lupien et al., 1998; Lupien et al.,
1994). More recently, we have also included specific
outcomes related to the damaged pathway in cardiovascular
disease and risk for myocardial infarction (e.g., nitric
oxide, fibrinogen). Fibrinogen, one of the blood-clotting
factors, has already been used as an allostatic load measure
in relation to job stress and socioeconomic status (Markowe
et al., 1985). Finally, outcomes related to other systems
such as the immune system have now been included.
Here, integrated measures of the immune response such
as delayed-type hypersensitivity (Dhabhar & McEwen,
1999) and immunization challenge (Kiecolt-Glaser, Glaser,
Gravenstein, Malarkey, & Sheridan, 1996) should reveal the
impact of allostatic load on cellular and humoral immune
function and help distinguish between the immunoenhanc-
ing effects of acute stress and immunosuppressive effects of
chronic stress. Moreover, assessment of the frequency and
severity of the common cold (S. Cohen et al., 1997; S.
Cohen, Tyrrell, & Smith, 1991) is another indirect way of
assessing immune function, and this might be considered a
secondary outcome.
Tertiary Outcomes. The tertiary outcomes are the
actual diseases or disorders that are the results of the allo-
static load that is predicted from the extreme values of the
secondary outcomes and of the primary mediators (see
Table 14.2). Thus far, the tertiary outcomes that are
thought to result from allostatic load are cardiovascular
disease, decreased physical capacity, severe cognitive de-
cline, and cancer.
With regard to the chronology of the allostatic load
model, it is important to note that in the allostatic load for-
mulation, the impact on health risk is thought to result not
only from large and clinically significant deviations from
normal operating ranges, but also from more modest dys-
regulations if they are present in multiple systems.
McEwen and Stellar (1993) hypothesized that the cumula-
tive impact on health risk from modest dysregulations in
multiple systems can be substantial, even if they individu-
ally have minimal and insignificant health effects.
Validation of the Allostatic Load Model
Although the concept of allostatic load offers a great op-
portunity to explain various stress-related disorders, the
model remains static as long as it has not been validated
with experimental data. It thus became important to assess
the predictive power of the allostatic load model in various
populations.

Allostatic Load and Aging. In a first validation
study, data were used from the MacArthur Successful
Aging Study that pertains to levels of physiologic activity
across a range of important regulatory systems, including
the HPA and sympathetic nervous systems as well as the
cardiovascular system and metabolic processes (Seeman
et al., 1994; Seeman & Chen, 2002; Seeman, McEwen
et al., 2001; Seeman, Singer, Rowe, Horwitz, & McEwen,
1997). In this study, Seeman and collaborators (Seeman,
Crimmins, et al., 2004) evaluated the capacity of an allo-
static load score to predict four categories of health out-
comes in 1,189 men and women aged 70 to 79 followed over
a period of 7 years. The measure of allostatic load used in
this first validation study reflected only one of the two as-
pects of physiologic activity postulated to contribute to al-
lostatic load, namely, higher, chronic, steady state levels of
activity related to the diurnal variation as well as any
residual activity reflecting chronic stress or failure to shut
off responses to acute stressors. The parameters that were
available for determining allostatic load scores included
urinary cortisol, adrenaline, noradrenaline; serum DHEA;
waist-hip ratio, diastolic and systolic blood pressure, glyco-
sylated hemoglobin, serum HDL, and total cholesterol. For
each of the 10 indicators of allostatic load, subjects were
classified into quartiles based on the distribution of scores
in the baseline cohort. Allostatic load was measured by
summing the number of parameters for which the subject
fell into the highest risk quartile, leading to an allostatic
load score for each participant. The results showed that
higher baseline allostatic load scores were associated with
significantly increased risk for 2.5-year (Seeman et al.,
1997) and 7-year (Karlamangla, Singer, McEwen, Rowe, &
Seeman, 2002; Seeman, McEwen et al., 2001) mortality, as
well as declines in cognitive and physical functioning,
and were marginally associated with incident cardiovascu-
lar disease events. More important, although none of the
10 components of allostatic load exhibited significant asso-
ciations on its own with health outcome, the summary
measure of allostatic load was found to be significantly as-
sociated with these four major health outcomes. These
findings were consistent with the idea that although a mod-
est deviation in the level of activity of a single physiologic
system may not be predictive of poor future health, the cu-
mulative toll from modest alterations in several physiologic
systems is a prognosis of poor health.
Allostatic Load across the Life Span. In a more re-
cent study, Crimmins and collaborators (Crimmins, John-
ston, Hayward, & Seeman, 2003) assessed age differences
in allostatic load from a large nationally representative
The Allostatic Load Model 589
sample in the United States. The National Health and Nu-
trition Examination Suvery involved the collection of data
over the period 1988 to 1994 in 18,000 individuals 20
years of age and older. Using the data from this study, an
allostatic load index was constructed using 13 indicators of
physiological dysregulation and analyzed using the quartile
method of Seeman and colleagues (Seeman, McEwen,
et al., 2001; Seeman et al., 1997). Results showed that allo-
static load score increased with age through the 60s and
then leveled off, so that individuals above 60 years of age
had fairly similar levels of allostatic load. The ratios of one
age group to the preceding showed that the increase in al-
lostatic load score from one age group to the next was .4 or
.5 in the first 2 decades of adulthood, and was .2 to .3 in
the next decades. The change in allostatic load score after
these decades (after 60 years) did not change significantly.
Although these results were not linked to subsequent
health outcomes, they revealed an interesting pattern of in-
creasing allostatic load score, starting in the early decades
of adulthood.
Allostatic Load and Work Conditions. Adverse
work characteristics and poor social support have been as-
sociated with an increased risk for cardiovascular disease
and other adverse health outcomes. To assess whether an
allostatic load index could be a good predictor of work
characteristics, Schnorpfeil and collaborators (2003) per-
formed a cross-sectional study with 324 industrial work-
ers in Germany. Psychosocial work characteristics were
assessed using various validated questionnaires, and an
allostatic load index was assessed using 14 physiological
components of the allostatic load model; the analysis was
performed using the quartile method (Seeman, McEwen
et al., 2001; Seeman et al., 1997). The results revealed
that older individuals, particularly men, had significantly
higher allostatic load scores than younger participants or
women. Of the various work characteristics evaluated,
only job demands related significantly with the allostatic
load score. This association persisted after controlling
for smoking status and gender and after excluding partic-
ipants reporting hypertension, cardiovascular disease, or
diabetes. However, the authors also showed that the
association between job demands and allostatic load was
highly dependent on age, with little or no association in
younger participants, and an increasing effect of job de-
mands on allostatic load score in participants over 45.
These results go along with the notion that allostatic
load results from the cumulative impact of wear and
tear that occurs throughout life and that adds up with in-
creasing age.
590 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
Allostatic Load and Socioeconomic Status. In a
more recent study, the data from the MacArthur Studies of
Successful Aging were used to assess whether the socioe-
conomic status (SES) differences in mortality can be par-
tially explained by differences in allostatic load (Seeman,
Crimmins, et al., 2004). Results showed that the score of al-
lostatic load explained 35.4% of the difference in mortality
risk between those with higher versus those with lower
SES. Of importance, it was shown that the cumulative
index provided independent explanatory power over and
above a measure of doctor-diagnosed disease. Here again,
the summary measure (allostatic load score) accounted for
more variance than individual biological parameters in pre-
dicting health outcomes, suggesting the high potential value
of this multisystem view of biological pathways through
which SES ultimately affects morbidity and mortality.
Allostatic Load and Social Support. Allostatic load
scores have not only been associated with negative out-
comes; new studies now show that the presence of social
support in an individual’s life is a strong predictor of low
allostatic load scores later in life. The first report of a sig-
nificant association between allostatic load score and so-
cial support was published by Singer and Ryff in 1999.
These authors used data from the Wisconsin Longitudinal
Study and searched for precursors to allostatic load
via ordered categories of cumulative adversity relative to
advantage over the life course. They operationalized life
trajectories via economic circumstances and social rela-
tionship experiences (e.g., parent-child interactions, qual-
ity of spousal ties). The results of this study revealed a
strong association between the extent of adversity early in
life and the likelihood of high allostatic load later in life.
More important, they showed that resilient individuals with
economic disadvantage but compensating positive social
relationship histories showed low prevalence of high allo-
static load. In 2001, using data from the MacArthur Study
of Successful Aging, Seeman and collaborators (Seeman,
Lusignolo, Albert, & Berkman, 2001) reported that greater
baseline emotional support in the participants of this longi-
tudinal study was a significant predictor of better cognitive
function at the 7.5-year follow-up, controlling for baseline
cognitive function and known sociodemographic, behav-
ioral, psychological, and health status predictors of cogni-
tive aging. Finally, in a recent study using data from the
Social Environment and Biomarkers of Aging Study in Tai-
wan, Seeman and collaborators (Seeman, Glei, et al., 2004)
examined relationships between social environment charac-
teristics and allostatic load in two groups of older Tai-
wanese individuals split as a function of age (54 to 70, and
71 and older). They used the longitudinal data on levels of
social integration and extent of social support as predictors
of cumulative allostatic load. The results showed that in the
54 to 70 age group, the presence of a spouse in early years
(6 to 8 years prior to the collection of data) was associated
with lower allostatic load in men, but not women. In the
older group of participants (71 years and above), it was
found that ties with close friends and/or neighbors were
significantly related to lower allostatic load score for both
men and women. Interestingly, although significant, these
relationships between social support and allostatic load
were more modest than the associations reported to occur
in Western societies. The authors suggested that contex-
tual, normative influences on social experience may affect
the patterns of association between features of these social
worlds and the physiological substrates of health.
Conclusion
Many important points result from our analysis of the allo-
static load model. First, cumulative wear and tear have ef-
fects on the body through lifelong exposure to various
challenges. Second, the data obtained so far show that allo-
static load tends to develop in time and increase sharply in
the later decades of adult life. These data also show that
environmental conditions, such as high job demands and
poverty, are associated with higher allostatic load scores.
However, the presence of social support, either in early
life or later in life, is a strong predictor of low allostatic
load. These results suggest that allostatic load is a process
that could begin very early in life, and that, depending on
the environmental conditions to which children are ex-
posed, they may develop an allostatic load process very
early in development.
In the next sections of this chapter, we summarize data
and concepts pertaining to the potential pathways by which
allostatic load can develop in children facing adversities.
EARLY ADVERSITY AND THE
DEVELOPMENT OF ALLOSTATIC LOAD
Following a definition by Sandler (2001), adversity can be
characterized as a condition that threatens the satisfaction
of basic human needs and goals (including physical safety,
self-esteem, efficacy, and social relatedness) and con-
strains the accomplishment of developmental tasks such as
school success and positive role functioning at home. Many
conditions have been related to early adversity, the most
important of them being low SES, child maltreatment, and
war. In the following, we discuss some data related to these

different types of early adversities. Although we are aware
that each type of adversity may have very different effects
on the body’s response to stress, it is important to note that
there have not been enough studies performed so far on this
particular issue to allow us to offer a clear distinction
across these different forms of adversity. Consequently, we
discuss these adversities generally as conditions very early
in life that threaten the satisfaction of a child’s basic needs
and goals (Sandler, 2001).
Many studies on adversity have looked at the effects of
low SES on health and well-being. It has been found that
individuals from high SES environments enjoy better
health than individuals from low SES environments. Vari-
ous studies have shown that blood pressure (Breier et al.,
1987) increases significantly as employment grade (B. S.
Dohrenwend, 1973), occupational status (Adelstein, 1980),
income (Folkman, Schaefer, & Lazarus, 1979), or years of
education (Adelstein, 1980) decrease. Although most of
the literature has concentrated on systemic diseases, other
studies have shown a significant relationship between SES
and mental health. For instance, inverse associations have
been reported between SES and the prevalence of Schizo-
phrenia, Posttraumatic Stress Disorder, Major Depression,
alcoholism, substance abuse, Antisocial Personality Disor-
der, and nonspecific distress (B. P. Dohrenwend, 2000).
With regard to developmental pathways, the exposure to
adverse conditions in childhood is closely related to the de-
velopment of physical and mental health problems in adult-
hood (Sandler, 2001). The relationship is of a cumulative
nature; that is, the greater the number of adverse experi-
ences, the more likely is development of a variety of prob-
lems later in life. For instance, Felitti et al. (1998) reported
a 4- to 12-fold increased risk for alcoholism, drug abuse,
depression, and suicide attempts in adults who had experi-
enced four or more adversities in childhood.
Although the relationship between early adversity and
health is well documented, the mechanisms that account for
the relationship are not clearly understood (e.g., Sandler,
2001). One possible pathway that links adversity to health
problems is stress (e.g., Lupien, King, Meaney, & McEwen,
2001; McLoyd, 1998). As stated earlier, adversity is a
condition that threatens the satisfaction of basic human
needs. The consequence of perceiving such a threat is a
state of stressful arousal (e.g., Sandler, 2001). With re-
spect to SES, it has been shown that low SES individuals
are exposed to a greater amount of chronic and acute
threats/stressors than high SES individuals (e.g., Bradley
& Corwyn, 2002). Environmental as well as social /psycho-
logical factors contribute to the increased stress levels.
With regard to environmental factors, low SES is associ-
Early Adversity and the Development of Allostatic Load 591
ated with poor living conditions, overcrowding, exposure to
environmental hazards, and crime (e.g., Bradley & Cor-
wyn, 2002; Haan, Kaplan, & Syme, 1989). With regard to
sociological /psychological factors, it has been shown that
lower SES increases the likelihood of exposure to negative
events such as social aggression, family conflict, and risk
behaviors (B. S. Dohrenwend & Dohrenwend, 1970). Addi-
tionally, low SES individuals are exposed to a higher rate
of change and instability in their lives such as family disso-
lution and household moves. This instability has been
found to produce a higher level of individual distress in
these individuals (Broadhead et al., 1983; B. S. Dohren-
wend & Dohrenwend, 1970). Moreover, individuals who
have access to psychological and material support from
family, spouses, or friends during stressful events appear
to be in better health compared to individuals without sig-
nificant support (Broadhead et al., 1983; S. Cohen, 1988;
Schwarzer & Leppin, 1989; Starfield, 1982). Individuals
low on the SES hierarchy have fewer of these social and
psychological resources to cope with stressful life events
than individuals higher in the SES hierarchy (S. Cohen,
1988; House et al., 1994; McLeod & Kessler, 1990).
To assess whether the development of the relationship
between SES and mental health is sustained, at least in
part, by exposure to high levels of glucocorticoids, Lupien
and collaborators (Lupien, King, Meaney, & McEwen,
2000; Lupien et al., 2001) measured morning salivary cor-
tisol levels and cognitive function (memory, attention, lan-
guage, and emotional processing) in 396 children (from 6
to 16 years of age) from low versus high SES in the Mon-
treal area in Canada (Lupien et al., 2001). Depressive
symptomatology and exposure to stressful events were also
assessed in each child’s mother through a semistructured
phone interview. The results revealed that low SES chil-
dren from 6 to 10 years old presented significantly higher
salivary cortisol levels when compared to children from
high SES. This difference disappeared at the time of school
transition, that is, at 12 years old, and no SES differences
were observed at 12, 14, and 16 years of age. The absence
of SES differences in cortisol levels during high school
could be due to changes in cortisol secretion in relation to
social roles (importance of peers over family, youth cul-
ture, etc.; see Lupien et al., 2001), or to the fact that those
teenagers from low SES who were available to perform
this study were the most resilient, that is, were those
teenagers who decided not to quit school. Neuropsychologi-
cal data showed that although children from low and high
SES do not differ with regard to memory, attentional, and
linguistic functions, children from low SES (at all ages)
presented a significantly higher level of negative emotional
592 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
processing (Lupien et al., 2005). Scores on the depression
and stress questionnaires were significantly higher for low
SES mothers, when compared to high SES mothers. More
important, the authors reported a significant positive cor-
relation between the mother’s depressive symptomatology
and her child’s cortisol level (Lupien et al., 2000). This
showed that the higher the score of the mother on the de-
pressive scale, the higher the cortisol level of her child. Al-
together, these results showed that low SES in young
children is related to increased cortisol secretion and nega-
tive emotional processing. Moreover, they showed that de-
pression in the mother is, in conjunction with low SES, a
significant factor predicting high cortisol levels in children.
Other studies have reported a significant association be-
tween early adversities and/or mother’s depression on a
child’s glucocorticoid levels. For example, numerous retro-
spective studies of adults and children have shown that
increased reactivity of the HPA system is associated with
early trauma (Cicchetti & Rogosch, 2001; Heim et al., 2000;
Kaufman et al., 1997; Yehuda, Halligan, & Grossman,
2001), as well as severe deprivation (Gunnar, Morison,
Chisholm, & Schuder, 2001). Moreover, studies of infants
and toddlers suggest that maternal postpartum depression
and behaviors, with the insecure mother-child attachments
that can result from these conditions, are positively associ-
ated with children’s cortisol levels (Field, 1994; Spangler &
Grossmann, 1993). In a longitudinal study of children of de-
pressed mothers, Hessl and collaborators (1998) found that
postpartum depression was positively associated with chil-
dren’s cortisol at 3 years of age, although another study re-
ported no effect of maternal depression on cortisol levels
when the children were age 7 (Ashman, Dawson, Panagi-
otides, Yamada, & Wilkinson, 2002).
However, in another study, Essex and collaborators
(Essex, Klein, Cho, & Kalin, 2002) measured salivary cor-
tisol levels in 282 children age 4.5 years and 154 of their
siblings. The authors were able to obtain maternal reports
of stress when the children were ages 1, 4, and 12 months
and again at 4.5 years. Finally, they assessed the child’s
mental health symptoms in the first grade of school. In the
first cross-sectional analysis of the association between ac-
tual maternal stress and the actual child’s cortisol levels,
Essex and collaborators found that at 4.5 years of age, the
children exposed to high levels of concurrent maternal
stress presented significantly higher cortisol levels than
children exposed to moderate or low levels of maternal
stress. Very interestingly, they also revealed a similar asso-
ciation of exposure to concurrent maternal stress and corti-
sol levels in the siblings of these children. The analysis of
the longitudinal data revealed that the children who were
exposed to high levels of concurrent actual maternal stress
and who were initially exposed to high maternal stress in
infancy (thus exposed to high maternal stress both in in-
fancy and at 4.5 years of age) were the only group that had
significantly higher cortisol levels. No effects of maternal
stress on child’s cortisol levels were observed for children
exposed to maternal stress in infancy only. These results
suggest that exposure to concurrent maternal stress is asso-
ciated with increased cortisol levels only for children
whose exposure began in infancy. The authors then ad-
dressed the potential association between child’s cortisol
levels and behavioral problems. Results showed that the
preschoolers with high cortisol levels presented greater in-
ternalizing and externalizing symptoms when assessed 2
years later. Finally, the link reported between low SES and
higher cortisol levels in children (Lupien et al., 2001) was
replicated in this study.
In a more recent study, G. W. Evans and Marcynyszyn
(2004) analyzed cross-sectional data from 216 third-
through fifth-grade low- and middle-income children
in upstate New York. The data of this study included
overnight urinary neuroendocrine levels, noise levels, res-
idential crowding (people per room), and housing quality.
The authors calculated an index of cumulative environ-
mental risk exposure based on the number of risk factors
(i.e., crowding, indoor noise, and housing quality). Risk
exposure for each factor was designated as greater than 1
standard deviation above the mean and given a score of 1.
The other exposure levels were considered lower risk and
coded as 0. The results revealed that cumulative environ-
mental risk exposure was significantly greater for low-in-
come children. More important, the authors showed that
cumulative environmental risk was positively correlated
with elevated overnight epinephrine, norepinephrine, and
cortisol in the low-income sample but not in the middle-in-
come sample. These results remained significant after
controlling for income, maternal education, family struc-
ture, age, and gender.
Altogether, these results strongly suggest that early ex-
posure to adversity (through low SES, maternal stress/de-
pression, or maltreatment) can have potent and long-lasting
effects on the secretion of glucocorticoids in children. Al-
though these studies provide very interesting results with
regard to the influence of early adversities on a child’s
basal cortisol levels, they do not provide an answer to a very
important question about the allostatic load model: What
determines the initial processing of an information as being
threatening ( leading to the secretion of the primary stress
mediators) or nonthreatening? Indeed, as we have dis-
cussed in previous sections, various situations can be real

threats (a house on fire) or implied threats (interpretation
of a situation as being novel and/or unpredictable and/or
uncontrollable), and both types of stressors will lead to the
activation of primary stress mediators and potentially to
allostatic load. It is thus becoming extremely important to
understand the mechanisms by which early adversities
might shape a child’s cognitive processing and lead to a
healthy or biased processing of incoming information and,
consequently, to cumulative allostatic load due to repeated
activation of the primary stress mediators when situations
are interpreted most of the time as being stressful.
The Subjective Nature of Reality: The Human
Information-Processing System
Cognitive psychology is concerned with how people per-
ceive, learn, remember, and think about information. Since
the 1960s, the human brain has often been conceptualized
as an information-processing device. From studies in cog-
nitive psychology, we have learned that what we perceive is
not an exact replica of the external world. Instead, percep-
tual processes transform and interpret information from
the external world. Additionally, our mental capacities are
limited, and to further process information, we have to al-
locate our mental resources to certain stimuli, a process
called selective attention. Stimuli we attend to enter a
short-term or working memory store; from there, some of
the information will eventually be transferred into long-
term memory, the memory system that stores our experi-
ences (episodic memory) and factual knowledge (semantic
memory; for criticism and modifications of this view of
memory, see, e.g., Baddeley, 1999, chap. 2). The content of
the long-term memory store will also determine how the
incoming information is interpreted and what behavioral
responses are elicited. In sum, what has become clear is
that incoming information is modulated at every stage of
the information-processing flow, finally resulting in an in-
dividual’s very own construction of reality.
The aspects of a situation an individual attends to, the
interpretation of these aspects, and the behavioral re-
sponses that follow are largely determined by the individ-
ual’s history and previous experiences. It can be assumed
that the cognitive systems are largely “shaped” during
childhood (e.g., Cicchetti, 2002), when those neurological
systems (frontal lobe, amygdala, and hippocampus)
undergo major developmental changes that subserve atten-
tion and memory as well as other higher-order cognitive
processes such as problem solving and decision making.
In the following, we describe cognitive processes that
we think can explain parts of the association that has been
Early Adversity and the Development of Allostatic Load 593
found between adversity and allostatic load/ health dam-
age. We introduce an information-processing model of
adaptation to threatening information that highlights two
different adaptation pathways that can lead to allostatic
load. We argue that both pathways are likely to be found in
individuals who grew up in disadvantaged and/or adverse
environments and who lacked protective mechanisms that
could counteract the influence of adversity.
An Information-Processing Model of Adaptation to
Threatening Information
As described earlier, individuals growing up in disadvan-
taged environments frequently face threatening situations:
instability, financial problems, limited residential choices,
crime, conflict, social aggression, and so on. Some of these
threats constitute absolute stressors (e.g., maltreatment,
crime); others constitute relative stressors (e.g., instabil-
ity, financial problems). As presented in Figure 14.2, the
frequent encounter with threatening information will likely
result in a cognitive system that reacts hypersensitively to
threatening information. This is accomplished by an atten-
tional system that is highly vigilant, because the individual
is expecting threatening information. The expectation of
threats and a bias toward interpreting situations as threat-
ening is probably due to a memory system that contains a
variety of highly interconnected and easily accessible
threat-related information (Pollak & Sinha, 2002). A cog-
nitive system that is biased toward the detection and pro-
cessing of threatening information can be viewed as
adaptive in the short run (allostasis), because an early and
Disadvantaged environments
Frequent encounter with threatening information
Sensitization Habituation
Hypersensitivity Hyposensitivity
to possible threats to possible threats
High vigilance Low vigilance
Low High anxiety Low anxiety Low
protective High responsiveness Low responsiveness protective
mechanisms to real and to real and mechanisms
fictive threats fictive threats
Maladaptive behavior
Allostatic load
Figure 14.2 Schematic representation of how early adversity
can modify the processing of threatening information, leading
to habituation or sensitization of detection of threatening
information.
594 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
facilitated threat detection might give individuals the nec-
essary time to counteract the threat (Pollak & Sinha, 2002).
This cognitive system, however, has at least two drawbacks
in the long run. First, a hypervigilant system is likely to
wear out quickly (allostatic load; McEwen, 1998b). Sec-
ond, the cost of high vigilance is false alarms to relative
stressors; that is, nonthreatening information might be
falsely identified as threatening (Pollak & Kistler, 2002).
Protective mechanisms, such as well-functioning parent-
child relationships and cognitive abilities, are often com-
promised as a consequence of adversity. If protective
mechanisms fail, sensitization to threatening information
is likely to result in maladaptive psychological (e.g., stress,
anxiety) and behavioral (e.g., aggressive, health-damaging)
responses (e.g., Masten, 2001). Prolonged states of anxiety
and anticipation of negative events can result in allostatic
load (McEwen, 1998b).
One can think of another, and in some sense opposite
way of dealing with frequent exposure to threatening infor-
mation, namely, habituation (see Figure 14.2). Habituation
is the tendency to become accustomed to a stimulus,
resulting in the stimulus becoming less and less noticed.
Individuals from disadvantaged environments might get ac-
customed to threatening situations and might filter out
threatening stimuli. This can be adaptive in the short run,
because the individual will be less anxious and less vigilant
(allostasis). On the other hand, the late detection of and the
general hyporesponsiveness to real threats prevent individ-
uals from proactive planning of adequate responses.
The consequence is that no stress response is initiated in
situations where such a response would be adequate. The
inadequate response of allostatic systems is one pathway
that has been linked to allostatic load (Type 4 allostatic
load, inadequate response; McEwen, 1998b). Furthermore,
the hyporesponsiveness to threatening information might
promote risk-taking and thrill-seeking behaviors that can
lead to further health damage and greater allostatic load,
especially when protective mechanisms fail.
Next, we review some empirical evidence for the adap-
tive processes described in the model. We describe studies
that demonstrate the specific influence that adversity has
on the development of several cognitive processes, includ-
ing attention, perception, memory, language, and theory of
mind. The research reviewed here comprises a rather het-
erogeneous set of studies covering very different aspects of
adversity, from low SES to different kinds of child mal-
treatment. We are aware of the fact that different experi-
ences lead to very specific outcomes. The heterogeneous
sample of studies we describe serves the purpose of illus-
trating how the environment shapes cognitive processes in
such a way that the individual is more susceptible to stress,
and is not meant to give a comprehensive overview of the
complex literature on adversity and cognitive development.
Throughout the chapter, the reader should keep in mind
that high adversity alone has only a weak predictive value
for poor developmental outcome. Only the combination of
high adversity and weak protective resources leads to mal-
adaptive profiles (Masten, 2001).
Before describing the studies, we briefly review the
brain structures that are involved in the stress response and
that might therefore be modified by early adversities.
These brain structures play an important role in interpret-
ing situations and selecting possible responses.
Brain Structures Involved in the Stress Response
Three brain structures are critically involved in the stress
response: the prefrontal cortex, the amygdala, and the hip-
pocampal formation. Each of these brain structures is af-
fected by stress hormones and/or involved in the regulation
of stress hormone secretion. At the same time, these brain
structures play a crucial role in the interpretation of a situ-
ation (as being stressful) and in the subsequent selection
and inhibition of possible responses.
The prefrontal cortex is sometimes described as the
highest part of the brain as it is involved in most higher cog-
nitive functions such as reasoning, planning, attention,
working memory, and some aspects of language (e.g., Con-
nolly, Goodale, Menon, & Munoz, 2002; Owen, Doyan,
Petrides, & Evans, 1996). For instance, the prefrontal cor-
tex determines which information will be considered and
which information will be inhibited during the perfor-
mance of goal-directed behaviors (e.g., Bunge, Ochsner,
Desmond, Glover, & Gabrieli, 2001). It also plays an im-
portant role in retrieval processes, especially in recalling
the temporal order and source of memories (e.g., Fan,
Snodgrass, & Bilder, 2003). Many other specific functions
of the prefrontal cortex could be named. Because of its in-
volvement in nearly all higher cognitive processes, some
authors regard the prefrontal cortex as the “ frontal moral
guidance system” that regulates social /moral behaviors
(e.g., Bigler, 2001, p. 610).
The amygdala is critically involved in assessing the
emotional significance of events (e.g., Anderson & Phelps,
2001). It is especially important for the processing of the
emotions of anger, aggression, and fear. Recent studies
with rats suggest that the amygdala also plays a crucial role
in forming associations between cues and outcomes
(Schoenbaum, Setlow, Saddoris, & Gallagher, 2003).
The hippocampal formation is involved in learning and
memory. It specifically subserves the formation and re-

trieval of episodic memories, that is, the human ability to
mentally travel back in time and remember where (spatial
component) and when (temporal component) a specific event
occurred (e.g., Tulving, 2002). During encoding, the hip-
pocampal formation is engaged in relational learning mecha-
nisms that bind the different components of an event into an
integrated memory trace (e.g., Davachi & Wagner, 2002).
Damage to the hippocampal formation results in profound
amnesia, especially an inability to remember new episodes
(e.g., Vargha-Khadem et al., 1997).
Roughly speaking, the described brain structures are
critically involved in evaluating a situation and selecting an
appropriate response (prefrontal cortex) with regard to the
emotional content of the situation (amygdala) and in rela-
tion to past experiences ( hippocampal formation, pre-
frontal cortex).
Selective Attention to Threatening Information in
Maltreated Children
As described earlier, it is impossible to process all informa-
tion to which an individual is exposed because attentional re-
sources are limited. Therefore, some environmental cues are
filtered out or attenuated and other stimuli are selected for
further processing (e.g., Treisman, 1964). Which stimuli are
attended to is a function of the physical and psychological
state of the individual, as is the saliency of these cues. Chil-
dren’s information-processing capacities are much more lim-
ited than those of adults (e.g., Case, 1985). Therefore, they
are much more selective in their attentional processes. Pollak
and Sinha (2002) argue that children selectively attend to
those features of the environment that are closely linked with
highly positive or highly negative outcomes.
Pollak and colleagues (Pollak, Cicchetti, Hornung, &
Reed, 2000; Pollak & Tolley-Schell, 2003) have demon-
strated in several studies using a variety of methods that
early experiences shape attentional processes and deter-
mine which stimuli children select for attention. They
found that maltreated and nonmaltreated children differed
in their attention allocation to certain emotional stimuli.
Specifically, physically abused children were highly sensi-
tive to information that signals threat and possible harm,
namely, angry facial expressions. At the same time, these
children had problems shifting their attentional focus away
from angry faces; that is, they had less control over their at-
tentional processes than nonabused controls.
Physically abused children are not only especially sensi-
tive to anger cues, they also experience more fear than
nonabused controls when witnessing angry interactions. For
instance, in a study by Hennessy, Rabideau, Cicchetti, and
Cummings (1994), physically abused children reported
Early Adversity and the Development of Allostatic Load 595
more fear than nonabused controls when watching video-
tapes of adults in angry interactions. Over time, the frequent
experience of fear and the accompanying stress response
can result in allostatic load (e.g., McEwen, 1998b).
It is important to note that the studies by Pollak and col-
leagues (2000) show that abused children do not experience
a general attentional deficit. Rather, abused children’s at-
tention is biased toward the detection of anger cues. Addi-
tionally, abused children have difficulties exerting control
over their attentional processes when faced with threaten-
ing information. In the next section, we describe how this
sensitization to threat affects perceptual and memory
processes in abused children.
Effects of Adversity on Perceptual and
Representational Systems
As described earlier, the long-term memory store contains
an individual’s knowledge about the world and past experi-
ences. It can be hypothesized that the long-term memory
store differs greatly in its content for children facing
adversities when compared to children in less adverse con-
ditions. Whereas children living in adverse conditions
may experience a lot of stressful situations and daily has-
sles and acquire a lot of factual knowledge about how to
survive in threatening environments, children living in
more favorable conditions may experience a great variety
of nonstressful situations. Thus, it can be assumed that the
memory content of children facing adversity is biased to-
ward threatening/stressful information. It can be further
speculated that children facing adversity are more likely to
interpret a situation as threatening and to select threat-ori-
ented coping strategies, whereas children living in more fa-
vorable conditions are more likely to interpret a situation
as nonthreatening and to select a nonthreat strategy to meet
the situational demands.
The assumption that memory processes are shaped or
fine-tuned by early experiences is again supported by the
work of Pollak and colleagues (Pollak et al., 2000; Pollak &
Sinha, 2002), who studied emotion recognition in children.
Pollak et al. presented physically abused, neglected, and
nonmaltreated children with several emotional stories. After
hearing each story, the children were shown photographs de-
picting facial expressions of different emotions and were
asked to select the photograph that would best fit what the
story’s protagonist felt. Neglected children, who have expe-
rienced a lack of care and responsiveness from their parents,
had difficulties recognizing different emotional states. In
contrast, physically abused children were as sensitive as
controls in differentiating emotions, and they performed es-
pecially well in recognizing anger-related situations. Both
596 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
maltreated groups showed a response bias: Neglected chil-
dren displayed a response bias for sad facial expressions, and
physically abused children showed a tendency toward select-
ing angry facial expressions. This study clearly shows that
early experiences shape how individuals interpret emotional
signals in a very specific way. For instance, the response
bias for anger in physically abused children might be due to
their experience of frequent anger outbursts that are often
unpredictable and that appear not to be related to the spe-
cific situation.
Physically abused children do not only show a response
bias for anger. Already at a perceptual level, these children
are especially sensitive to anger cues. This was experimen-
tally shown by Pollak and Sinha (2002), who asked physi-
cally abused and nonabused children to recognize emotions
from degraded pictures of happy, angry, sad, and fearful
faces in a priming task. Faces were initially presented in
highly degraded formats. Over time, the pictures became
more organized and easier to identify. Physically abused
children were able to correctly identify angry facial expres-
sions on the basis of more degraded picture versions than
were nonmaltreated children. Physically abused children
needed more information than controls to recognize sad-
ness. No group differences were found for happiness or
fearfulness.
Taken together, these studies show that an abusive envi-
ronment makes children especially sensitive for the detec-
tion of anger. According to Pollak and Sinha (2002), this is
accomplished by a memory system that is fine-tuned by
early experiences to allow for facilitated access to the rep-
resentation of anger. Physically abused children grow up in
an environment that is characterized by uncontrollable sud-
den outbursts of violence. The early detection of anger
might give children additional time to prepare for hostile
interactions. In this sense, abused children’s early detec-
tion of threatening information can be viewed as adaptive.
However, it becomes maladaptive when premature deci-
sions about facial expressions are made (see Pollak &
Sinha, 2002, for these arguments). In cases of uncertainty,
abused children tend to interpret facial expressions as
angry, a bias that restricts them from considering other
possible interpretations (Pollak & Kistler, 2002). Later in
life, a bias toward interpreting situations as threatening
and therefore stressful is likely to result in allostatic load
and situational-inadequate responses such as conduct dis-
orders, aggressive behavior, depression, and anxiety.
Effects of Adversity on Language Development
Interpersonal communication is one mechanism that helps
individuals to cope with stressful situations. This coping
mechanism is often spontaneously used with family and
friends, and it is a basic element of many psychological coun-
seling approaches (e.g., client-centered therapy; Rogers,
1951). For this coping mechanism to work, individuals need
to be able to verbally express their problems and feelings;
that is, communicative skills play an important role.
Language develops in a very constrained and pre-
dictable way in all normally developing children, and
many researchers have emphasized the biological-matura-
tional component of language acquisition (e.g., Chomsky,
1972; Pinker, 1994). This component might explain why
individuals reared in very different cultural and linguistic
environments all acquire their native language. Although
almost all individuals become fluent speakers, environ-
mental factors likely influence the grade of linguistic
proficiency that is reached. It has been shown that disad-
vantaged environments can influence the pathways of lan-
guage acquisition, possibly resulting in language and
communicative deficits later in life. For instance, children
from lower SES families show slower rates of vocabulary
growth than children from higher SES families (Hoff,
2003). This effect is mediated by the speech children hear
at home. Hoff showed that the speech of mothers from
lower and higher SES differs in quantity, lexical richness,
and sentence complexity, and that these differences ex-
plained over 20% of the variance in 2-year-olds’ size of
productive vocabulary.
Cicchetti and colleagues (Beeghly & Cicchetti, 1994;
Coster, Gersten, Beeghly, & Cicchetti, 1989) looked at lan-
guage development in maltreated children and found delays
in language structure, expressive vocabulary, and expres-
sion of internal states. Eigsti and Cicchetti (2004) extended
these findings by showing that not only the content but also
the linguistic form is affected by maltreatment and SES: 5-
year-old maltreated children and nonmaltreated children
from low SES both scored below age-expected levels of
syntactic abilities, with maltreatment causing a signifi-
cantly greater amount of developmental delay.
What are the long-term effects of these developmental
delays? Because longitudinal studies are missing, there is
no definite answer to that question. However, Eigsti and Ci-
cchetti (2004) suspect that language delays lead to later
emotional, social, and cognitive delays and exacerbate ex-
isting problems. The observation that the speech of moth-
ers from lower and higher SES differs in many aspects
(Hoff, 2003) further supports long-lasting detrimental ef-
fects of disadvantaged environments on language skills.
The less an individual is able to communicate his or her
problems and internal states, the more difficulties he or she
might have coping with stressful situations, because inter-

personal communication might not lead to the desired
stress-releasing effect.
Effects of Adversity on False Belief Understanding
A 3-year-old child’s understanding of the mind is very
different from that of a 5-year-old child. Whereas 3-year-
old children roughly assume that all people share the same
knowledge, 5-year-old children have realized that peo-
ple’s beliefs may be true or false and that people’s behav-
ior is based on these beliefs rather than on reality. In their
now-classic set of experiments on false belief understand-
ing, Gopnik and Astington (1988) showed children of dif-
ferent ages a box with pictures of candy on it and asked
the children what they thought was in the box. The chil-
dren assumed that the box contained candy and were sur-
prised when they opened the box and found crayons.
When asked what another child who has not yet looked in-
side the box would think was in the box, 5-year-old chil-
dren seemed to understand the concept of deception and
said “candy.” Three-year-old children, in contrast, an-
swered that the other child would think that the box con-
tained crayons. Moreover, 3-year-old children also denied
their own original deception; that is, they said they had al-
ways thought that the box contained crayons. Since the
original work by Gopnik and Astington several studies
have shown that major changes in false belief understand-
ing take place around 4 years of age (Wellman, Cross, &
Watson, 2001).
Does false belief understanding follow a different devel-
opmental pattern in maltreated children? In a recent study
by Cicchetti and colleagues (Cicchetti, Rogosch, Maughan,
Toth, & Bruce, 2003), 3- to 8-year-old maltreated and non-
maltreated children performed two false belief tasks.
Among children with a verbal mental age of 49 months or
greater, maltreated children demonstrated less false belief
understanding than nonmaltreated children. Performance
was worst for children who were physically abused and
whose maltreatment started during the toddler years. Cic-
chetti et al. suggest two possible pathways by which mal-
treatment can affect false belief understanding. First,
deficits in caregiving, especially the lack of parental empa-
thy and sensitivity to the child’s internal experiences, and
the limited communication of feelings and emotions by
the parents may contribute to a delay in the child’s under-
standing of beliefs of self and others. This suggestion is
strengthened by studies showing that maternal language
to toddlers about internal states mirrors their children’s
abilities to become increasingly other-oriented (Beeghly,
Bretherton, & Mervis, 1986; J. Dunn, Bretherton, Munn,
1987). Dunn and collaborators (J. Dunn, Brown, & Beard-
Early Adversity and the Development of Allostatic Load 597
sall, 1991) found that individual differences in the amount
of family discussions about feelings and emotions pre-
dicted young children’s understanding of other people’s
feelings and beliefs, even when children’s language skills
were controlled for analytically. From these results, it is
becoming clear that a child does not necessarily need to be
exposed to significant adversities (e.g., maltreatment) in
order to present weaknesses in the development of verbal
abilities and emotional understanding, but that exposure to
a family environment lacking the richness of interactions
necessary to develop these skills may be sufficient to pre-
vent adequate cognitive and emotional abilities later in life.
Also, given the fact that the ability to make judgments
about mental states is critical to social interactions, it may
be possible that a lack of adequate development of this skill
may prevent children from coping efficiently in the face of
the various stressors of life.
Second, neurobiological maturation processes might be
more directly altered by maltreatment in that “children
subjected to pathological care giving may acquire neu-
ropathological connections instead of functional neural
connections” (Cicchetti et al., 2003, p. 1087). This path-
way could explain why an onset of maltreatment during the
toddler years is especially detrimental to the development
of false belief understanding, because the toddler period is
a time of rapid creation and modification of neuronal con-
nections (see also Cicchetti, 2002), and many of the pre-
cursors of false belief understanding develop during that
period, for example, language development (especially the
verbal expression of internal states), conceptual develop-
ment, increased individuation, and self-other differentia-
tion (Cicchetti, 1991).
Regarding the influence of SES on theory of mind de-
velopment, findings are somewhat mixed. For instance,
Cutting and Dunn (1999) found differences in false belief
understanding in relation to parental occupational class
and mother’s education (see also Pears & Moses, 2003).
Other researchers have found that SES and performance in
theory of mind tasks were not (Cicchetti et al., 2003) or
only weakly (Murray, Woolgar, Briers, & Hipwell, 1999)
related and that parental behaviors (Hughes, Deater-
Deckard, & Cutting, 1999) or general and verbal intelli-
gence (Murray et al., 1999) were better predictors of
theory of mind performance.
Taken together, studies have shown that adversity can
alter false belief understanding and other aspects of theory
of mind development in children. For the case of maltreat-
ment, the pathways through which maltreatment con-
tributes to developmental delays have been specified. For
low SES, the literature is less clear and the multifaceted
598 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
factors that may lead to successful or unsuccessful devel-
opment need further specification.
Positive Outcome in the Context of Adversity: The
Concept of Resilience
Not everybody reared in disadvantaged environments will
face problems later in life. In the literature, the phenomenon
that similar stressful experiences can lead to very different
individual outcomes is referred to as multifinality (Curtis &
Cicchetti, 2003). At the same time, not everybody who expe-
riences problems later in life has faced adversity, a phenom-
enon referred to as equifinality (Curtis & Cicchetti, 2003).
Both concepts highlight the important fact that early experi-
ences do not ultimately determine further developmental
pathways. This brings us to the concept of resilience. Re-
silience can be defined as successful adaptation or compe-
tent developmental outcome in the face of risk and adversity.
Curtis and Cicchetti conceptualize resilience as “a dynamic
process that is influenced by neural and psychological self-
organization, as well as transactions between the ecological
context and the developing organism” (p. 776). Thus, many
different interdependent factors contribute to resilient func-
tioning, including biological factors such as genetic makeup,
brain organization, and neuroendocrine functioning; psy-
chological factors such as emotion regulation, attachment,
and locus of control; and environmental factors such as par-
enting (for overviews, see, e.g., Curtis & Cicchetti, 2003;
Luthar, 2003; Masten, 2001). Here, we focus on cognitive
processes that contribute to resilience.
An interesting longitudinal study on adversity and re-
silience was conducted by Masten et al. (1999), who fol-
lowed children over 10 years from childhood through
adolescence and assessed three major domains of compe-
tence: academic achievement, conduct, and peer social
competence. Adversity was measured as the occurrence of
major life events and experiences that are likely to be
stressful (e.g., death of a family member). The study fo-
cused on two possible resources that are assumed to protect
children from the effects of adversity: intellectual func-
tioning (intelligence) and parenting quality. The authors
found that both resources protected children from develop-
ing competence problems. High-adversity children with
high intelligence scores and well-functioning parent-child
relationships were as competent as low-adversity children.
At the same time, low-adversity children with low re-
sources developed competence similar to high-resource
children. This shows that only the combination of high ad-
versity and low resources resulted in competence prob-
lems. Specific to intellectual functioning, intelligence was
related to academic achievement and to social competence
in childhood. Academic achievement is negatively associ-
ated with mental health problems (Sandler, 2001). Most in-
teresting, high intellectual functioning in childhood was a
protective factor against developing conduct problems in
adolescence, thus pointing to the long-term moderating ef-
fect of early cognitive functioning on adversity. This find-
ing also replicates previous studies that have shown that
intellectual functioning is an important moderating vari-
able of antisocial behavior in high-risk groups (White,
Moffitt, & Silva, 1989). As Masten et al. (1999, p. 163)
point out, “Numerous processes could underlie this effect:
Good verbal, learning or problem solving aptitude could
play a role in assessing threat, accessing resources, effec-
tive seeking of healthier environments or relationships for
development, appealingness to teachers, etc.”
In summary, the data suggest that the capacity to detect
threatening and nonthreatening information develops very
early in life and is sensitive to environmental conditions.
This modification of the selective attention process will
lead to more threatening cues and information being stored
in long-term memory, with the resulting effect that when
the time comes to find a response to a threat (relative or ab-
solute, real or implied), a threat-related type of response
(aggression, violence, etc.) may be more readily available
for immediate action. Although this response may be adap-
tive in the short run, the frequent detection of threat and/or
threat response may lead to an allostatic load process, af-
fecting the behavior, the body, and the brain. In terms of
behavior, this decision process might lead in the long run to
the development of externalizing behaviors and/or a diag-
nosis of a Conduct Disorder. If this is the case, then some
bodily markers of allostatic load may be related to exter-
nalized behaviors in children.
To assess whether such a process might occur in devel-
oping children, we have reviewed the literature on external-
ized behavior and Conduct Disorders in children, in
association with biological processes known to be involved
in allostatic load. In our literature search, we found various
markers of allostatic load that have been studied in relation
to externalized behaviors or Conduct Disorders in children.
Some of these biological processes are primary stress me-
diators (cortisol, DHEAS), and others are secondary out-
comes (waist-hip ratio, cholesterol, and heart rate). We
summarize these data in the following sections.
Allostatic Load and Externalized
Behaviors/Conduct Disorder in Children
Conduct Disorder (CD) refers to a group of symptoms or
problematic externalized behaviors. The description of CD

in the Diagnostic and Statistical Manual of Mental Disor-
ders, fourth edition (DSM-IV), includes four types of be-
havior: (1) aggression toward people or animals, (2)
destruction of property, (3) deceitfulness or theft, and (4)
serious violations of rules; all of these are referred to as ex-
ternalizing behaviors. Because it is a very heterogeneous
disorder both in its occurrence and in its etiology, Frick
(1998) proposed using the plural term Conduct Disorders.
Two different types of CD are nowadays distinguished: the
childhood-onset (DSM-IV) or life-course-persistent type
(Caspi & Moffitt, 1995) and the adolescent-onset (DSM-
IV) or adolescence-limited type (Caspi & Moffitt, 1995),
each with a different etiology. The spectrum of CD also
includes more extreme forms of behaviors, such as psycho-
pathic behavior. It has been acknowledged that the distinc-
tion between these two types of CD is of importance for
their causal accounts and treatment decisions (Caspi &
Moffitt, 1995; Frick, 1998; Moffitt, Caspi, Harrington, &
Milner, 2002). In our review of allostatic load markers, we
focus on the childhood-onset or life-course-persistent type,
and we intermix by sections the results of studies that have
assessed either externalized behaviors in children or chil-
dren diagnosed with Conduct Disorders. However, for the
sake of clarity, we refer to only Conduct Disorders in each
section’s title.
Commonly, adverse environmental factors are suggested
to contribute, at least partially, to the onset, maintenance,
and exacerbation of externalizing behaviors among children
(Haapasalo & Tremblay, 1994; McLeod & Shanahan, 1993).
The adverse environmental conditions studied in relation
to externalizing behaviors include SES (Brooks-Gunn &
Duncan, 1997; McLoyd, 1998), low parental education at-
tainment (Hanson, McLanahan, & Thomson, 1997), negative
parental behaviors (Lempers, Clark-Lempers, & Simons,
1989), single motherhood (Corcoran & Chaudry, 1997), ex-
posure to violence (Miller, Wasserman, Neugebauer, Gor-
man-Smith, & Kamboukos, 1999), and low quality of
schools and neighborhoods (Bradley & Corwyn, 2002).
Here, it is important to note that the importance of these
environmental variables in the development of externalized
behaviors may stem from their actions on parental behavior.
For example, economic hardship may decrease the mother’s
self-esteem (McLeod & Nonnemaker, 2000) and the par-
ents’ investment in the child (Bolger, Patterson, Thompson,
& Kupersmidt, 1995; Jackson, Brooks-Gunn, Huang, &
Glassman, 2000), may induce frequent use of physical disci-
pline (Conger, Patterson, & Ge, 1995; Deater-Deckard,
Dodge, Bates, & Pettit, 1996), and may exacerbate moth-
ers’ depressive symptoms (McLeod & Nonnemaker, 2000).
So, the response that is induced by exposure to adverse en-
Early Adversity and the Development of Allostatic Load 599
vironmental factors may be mediated by the psychological
and physiological stress induced by these adversities, which
in turn may be responsible for enhanced propensity to
manifest externalizing behaviors (G. W. Evans, 2003; G. W.
Evans & English, 2002).
A child who manifests externalization problems may
react and cope (at physiological, cognitive, or behavioral
levels) differently when confronted by threats as a function
of his or her age. For example, a 10-year-old child with ex-
ternalization problems may decide to either fight or lie to
escape negative consequences, whereas an adolescent with
externalization problems may be prone to select dangerous
health-related behaviors (e.g., substance abuse, smoking)
or adopt risk behaviors such as antisocial behaviors (e.g.,
stealing, fighting), drop out of school, or engage in sensa-
tion-seeking activities. From society’s viewpoint, these
behaviors may be unacceptable or at least impede access to
better living conditions. Nevertheless, in the short run,
some of these behaviors may enhance the child’s or adoles-
cent’s perceived adaptation to threats by enhancing self-
esteem or offering an alternative access to prestige or
money, being recognized and respected, or having a thrill.
Furthermore, children and adolescents manifesting exter-
nalized behaviors may also elicit more negative interac-
tions and coercion from their environment. In attempting to
adapt to threats in a cost-effective way according to their
initial individual differences, some of them may exacerbate
the likelihood of negative reactions from the environment,
which could eventually lead to a sustained engagement in
externalizing behaviors (Brennan & Raine, 1997). Thus,
children with externalization problems may select differ-
ent coping strategies from children without these problems
as a result of both individual characteristics and adverse
environmental conditions.
General Cognitive/Brain Dysfunctions in
Conduct Disorders
The three brain structures (prefrontal cortex, amygdala,
hippocampal formation) that are involved in the stress re-
sponse (see earlier discussion) have been found to be struc-
turally and/or functionally different in individuals with
CD or other forms of antisocial disorders, including crimi-
nal psychopaths, when compared to normal controls.
With regard to structural differences, right temporal
and prefrontal lobe volumes were reported to be smaller
in early-onset CD and in Antisocial Personality Disorder
(APD; Kruesi, Casanova, Mannheim, & Johnson-Bilder,
2004; Raine, Lencz, Bihrle, LaCasse, & Colletti, 2000).
Bigler (2001) put forward the hypothesis that the prefrontal
cortex as the major instance of moral guidance never
600 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
developed a functional role in individuals with APD, thus
explaining the deficiency of moral decision making in
these individuals. It might be speculated that smaller pre-
frontal lobe volumes are also related to the impulsive be-
havior seen in individuals with CD and APD, because the
prefrontal cortex plays a major role in response inhibition.
With regard to functional differences, Kiehl et al.
(2001) showed that criminal psychopaths showed less acti-
vation of the amygdala and hippocampal formation when
processing affective stimuli in comparison to criminal
nonpsychopaths and controls. As described earlier, the
amygdala is critically involved in fear processing and the
formation of associations between cues and outcomes. The
lower affect-related amygdala activation in criminal psy-
chopaths therefore goes hand in hand with the finding that
psychopaths are insensitive to several types of fear and
punishment contingencies (e.g., Hare, 1965; Patrick et al.,
1994). At the same time, in the study by Kiehl et al., crimi-
nal psychopaths showed an overactivation in the prefrontal
cortex when processing affective stimuli. According to
Kiehl et al., this overactivation might imply that criminal
psychopaths need more cognitive resources to process af-
fective stimuli.
As discussed earlier, allostatic load is intimately linked
to brain integration of the environment. The interpretation
of events as threatening or not leads to behavioral re-
sponses selected to cope with the threat, which in turn
contribute to an increase of allostatic load in the long run
(McEwen, 2000b). Children experiencing externalizing
problems may modify in their own way (not necessarily
consciously) their information-processing system (e.g., se-
lection of coping behaviors and evaluation of their cost-ef-
fectiveness) to minimize the intensity/frequency of their
subsequent reactions to further threats at physiological, at-
tentional, and emotional levels. In other words, informa-
tion processes may act to inhibit relevant events initially
processed as threatening ( habituation). As a consequence,
physiological reactions induced by these initial threatening
events may be reduced, leading to an allostatic response
(inadequate response). This modification of the perception
of threat will likely influence the physiological response of
the child to environmental threats, which may then act
to enhance externalizing behaviors through higher toler-
ance to negative events (e.g., punishment, pain, emotional
arousal), reducing the child’s response to social rules and
frequent risky and sensation-seeking behaviors adopted by
the child in order to cope with physiological underarousal
(Raine, 1993).
We acknowledge that sustained externalizing problems
during childhood and adolescence are not exclusively in-
duced through modifications of brain chemistry. Yet, a
closer examination of the physiological markers related to
allostatic load is a challenging and promising way to under-
stand the mechanisms by which markers of allostatic load
may relate to externalizing behaviors.
Cortisol and Conduct Disorder
Among all the components of allostatic load, the primary
stress mediator cortisol has been the most widely studied in
relation to Conduct Disorders in children. To this day, the
most consistent finding with regard to the secretion of cor-
tisol levels in children with CD is the presence of lower
basal levels of cortisol, although some discrepancies in the
results are clearly observable. The first study of children
with CD was by Kruesi and collaborators in 1989 (Kruesi,
Schmidt, Donnelly, Hibbs, & Hamburger, 1989). They
measured 24-hour urinary cortisol excretion in 19 boys
with Attention Deficit and/or CD and 19 age-, race-, and
IQ-matched normal controls. The results revealed no dif-
ference in the 24-hour urinary cortisol secretion between
the two groups. However, 2 years later, McBurnett and col-
laborators (1991) assessed salivary cortisol levels in 67
boys (ages 8 to 13 years) with Anxiety Disorders and/or
CD. The results showed that children with both CD and
Anxiety Disorder had higher levels of salivary cortisol than
children with CD without comorbid Anxiety Disorder.
After this first report of significantly lower cortisol levels
in children with CD, a wealth of studies reported either a
negative correlation between cortisol levels and symptoms
of CD (McBurnett & Lahey, 1994; McBurnett, Lahey, Ca-
passo, & Loeber, 1996; McBurnett, Lahey, Rathouz, &
Loeber, 2000; Pajer, Gardner, Rubin, Perel, & Neal, 2001)
or the presence of significantly lower cortisol levels in chil-
dren with CD when compared to children without CD
(Pajer et al., 2001).
Although a significant number of studies have reported
a link between low cortisol levels and Conduct Disorders, it
is important to note that, similarly to Kruesi and collabora-
tors’ (1989) study, other studies did not report such an as-
sociation. For example, in 1997, Schulz and collaborators
(Schulz, Halperin, Newcorn, Sharma, & Gabriel, 1997)
tested plasma salivary cortisol levels in aggressive and
nonaggressive boys with Attention Deficit Disorder and re-
ported no differences in cortisol levels between the groups.
Other studies performed with adolescent mothers with CD
did not report the negative correlation between cortisol lev-
els and symptoms of CD (Susman et al., 1999) or did not re-
port a significant difference between cortisol levels in
adolescent mothers with or without CD (Azar et al., 2004).
The discrepancy observed in the literature on cortisol and

symptoms of CD may stem from a variety of factors, in-
cluding the diagnosis of CD, the externalizing behavior
measured, and the time and method of assessment of corti-
sol. Indeed, in the various studies that were performed on
the link between cortisol levels and Conduct Disorders, im-
portant methodological differences are observed, with
some authors assessing the 24-hour urinary pattern of cor-
tisol secretion (Kruesi et al., 1989), others assessing
plasma cortisol levels measured immediately to 115 min-
utes after insertion of a catheter (Pajer et al., 2001; Schulz
et al., 1997; Susman et al., 1999), and others assessing cor-
tisol in saliva samples taken in the morning period (Azar
et al., 2004; Vanyukov et al., 1993) or at any time (not con-
trolled for) over a 2-year period (McBurnett & Lahey,
1994; McBurnett et al., 1991, 1996, 2000).
Here, we remind the reader that basal levels of cortisol
follow a circadian cycle, with higher levels in the morning
and declining levels throughout the day. It is thus extremely
important when assessing cortisol levels in humans to con-
trol for the time of day at which the samples are taken.
Moreover, any cortisol difference pertaining to samples ob-
tained in the morning cannot be taken as direct evidence
that cortisol secretion is lower in children with Conduct
Disorders, given that it may be possible that the total excre-
tion of cortisol throughout the day is not different in these
children when compared to control children. Also, there is a
major difference between plasma and salivary measures of
cortisol, as the plasma concentrations of cortisol include
both the free ( biologically active) and bound (to carrier pro-
teins and thus inactive) portions of cortisol, whereas sali-
vary samples assess the free portion of cortisol. Given that
it is the free portion of cortisol that will be active, salivary
cortisol may represent a better measure of the biologically
active cortisol levels than plasma cortisol levels. Moreover,
cortisol levels have been shown to present a significant in-
crease at 30 and 60 minutes after waking (called the cortisol
awakening response; J. C. Pruessner et al., 1997), and this
pronounced cortisol increase during the first hour after
waking in the morning has been found to be associated with
higher measures of self-reported stress (J. C. Pruessner,
Hellhammer, & Kirschbaum, 1999; M. Pruessner et al.,
2003; Schulz, Kirschbaum, Pruessner, & Hellhammer, 1998;
Wüst, Federenko, Hellhammer, & Kirschbaum, 2000). Fi-
nally, venipuncture has been shown to induce a potent re-
sponse of the HPA axis (Meeran, Hattersley, Mould, &
Bloom, 1993), and it is possible that the cortisol response to
venipuncture induces large inter- and intraindividual corti-
sol responses, explaining some of the discrepant findings.
For a complete review of the methodological factors that
could account for the discrepancies of data and for more in-
Early Adversity and the Development of Allostatic Load 601
formation on the best method to assess cortisol levels in hu-
mans, see the recent review by Goodyer and collaborators
(Goodyer, Park, Netherton, & Herbert, 2001).
Be that as it may, some mechanisms have been proposed
to explain the link between low cortisol levels and external-
izing behaviors. Low cortisol levels noted in aggressive in-
dividuals are understood in the light of an underaroused
sympathetic autonomous nervous system and HPA axis
(Lahey, McBurnett, Loeber, & Hart, 1995). Consequently,
a dampened HPA axis secretion pattern would constitute
an adaptive response ( habituation) to aversive situations
such as pain and parental coercive behaviors (Vanyukov
et al., 1993). Moreover, lower reactive secretion in individ-
uals manifesting externalizing behaviors may be explained
as a higher HPA axis activation threshold (Kruesi et al.,
1989). For these individuals, moderate stressful events may
be inefficient to induce HPA axis activation. As a result,
those individuals may feel understimulated and be prone to
searching for sensation-seeking activities.
The low cortisol-CD link could also be interpreted as a
physiological marker of a tendency toward (or an absence
of ) behavioral inhibition (Kagan, Reznick, & Snidman,
1987). Gray (1982, 1987) suggested that two neurophysio-
logical systems are implicated in antisocial behaviors: the
behavior inhibition system (BIS) and the behavior activa-
tion system (BAS). The BIS has received considerable at-
tention in regard to the low cortisol levels noted in
externalizing individuals. One of the main functions of the
BIS is to down-regulate (inhibit) nonreinforced behaviors
(e.g., aggressive behaviors) while perceiving aversive cues
in the environment (e.g., punishment). BIS activation is ex-
pressed at the behavioral level through inhibition responses
and at the physiological level in cortisol, serotonin, and no-
radrenalin secretion (King, Barkley, & Barrett, 1998).
Convergent with the BIS, higher cortisol levels appear to be
a protective feature against manifesting externalizing be-
havior problems ( because facilitating inhibition of these
behaviors), and lower cortisol levels may be a marker of a
behavioral disinhibition already associated with external-
izing behaviors (King et al., 1998; McBurnett et al., 1996).
Interestingly, most studies assessing the association be-
tween cortisol levels and the development of disruptive
behaviors in preschoolers report a positive association be-
tween cortisol and some psychological correlates of exter-
nalizing behaviors (e.g., negative affect, aggression,
difficult or instable temperament; E. P. Davis, Donzella,
Krueger, & Gunnar, 1999; de Haan, Gunnar, Tout, Hart, &
Stansbury, 1998; Gunnar, Tout, de Haan, Pierce, & Stans-
bury, 1997). For example, Dettling, Gunnar, and Donzella
(1999) reported a positive association between cortisol
602 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
levels secreted during the day and negative affect and ag-
gression in preschoolers. To explain this result, they sug-
gested that immature regulation systems and negative peer
relationships might be correlated with higher cortisol se-
cretion. In this sense, the higher cortisol levels associated
with aggression in preschoolers may be related to a stress-
induced cortisol release rather than to basal levels of corti-
sol. Higher cortisol levels have also been interpreted as
a marker of the effort to adapt to a demanding and unfamil-
iar social environment (Stansbury & Harris, 2000). Even
though moderate cortisol secretion may enhance the child’s
capacity to cope with an unfamiliar environment, large se-
cretions of cortisol may be a marker of dysfunctional social
adaptation (McEwen, 2002). Consequently, an inverted U-
shape relationship between cortisol and social functioning
may best characterize this association in childhood (E. P.
Davis et al., 1999) and adulthood (McEwen, 2003).
In the preschool years, the mechanisms involved in the
modified HPA axis resulting from adverse environmental
conditions remain to be clarified. The first years of life
possibly constitute a sensitive period in which several
physiological systems complete their maturation and show
greater plasticity to environmental factors (De Kloet,
Vreugdenhil, Oitzl, & Joels, 1998; Gunnar & Donzella,
2002). Consequently, adverse environmental conditions ex-
perienced during this sensitive period may be particularly
determinant in inducing changes in the HPA axis (Heim
et al., 2000; Meaney et al., 1996). Essex, Klein, Cho, and
Kalin (2002) observed that children who experienced
chronic stress during their 1st year of life have higher cor-
tisol levels at 4.5 years of age, suggesting that cumulative
rather than acute stressful events are linked to permanent
physiological changes (G. W. Evans & English, 2002).
Modified HPA axis secretion patterns observed in child-
hood and adulthood are thought to be one of several physio-
logical outcomes of chronic stress experienced early in life
(Gunnar et al., 2001; Gunnar & Vazquez, 2001).
Dehydroepiandrosterone and Conduct Disorder
DHEA and its sulfate (DHEAS) is another primary stress
mediator that has been studied in relation to CD. The ra-
tionale here is that from around age 6, children exhibit a
gradual increase in androgens, but these androgens are of
adrenal origin, a period called the adrenarche. It is not until
puberty that gonadal androgens (of gonadal origin), such as
testosterone, become more important. Researchers (Buy-
dens-Branchey & Branchey, 2004; Dmitrieva, Oades,
Hauffa, & Eggers, 2001; Goodyer et al., 2001; van Goozen,
Matthys, Cohen-Kettenis, Thijssen, & van Engeland, 1998;
van Goozen, van den Ban et al., 2000) have thus concluded
that studies of Conduct Disorders in prepubertal children
should therefore not focus on testosterone, but on adrenal
androgens, such as DHEA and DHEAS. DHEA and
DHEAS are also very interesting for the study of Conduct
Disorders because, besides being secreted in the adrenal
glands, they are also endogenously synthesized by the brain
(Robel & Baulieu, 1995). Many studies have shown that
DHEA acts by increasing neuronal excitability, enhancing
neuronal plasticity and having neuroprotective properties
(Wolf & Kirschbaum, 1999). From the effects of DHEA on
the body and the brain, many authors have suggested that
DHEA / DHEAS should be elevated in individuals who are
aggressive. This suggestion has been confirmed.
In a study performed in 1998, van Goozen and collabo-
rators examined the relationship between plasma levels of
testosterone and DHEAS in 15 boys with CD and 25 nor-
mal controls boys. The intensity of aggression and delin-
quency of the boys were rated by parents and teachers over
a period of 6 months. The results showed that boys with CD
had significantly higher levels of DHEAS, although testos-
terone levels did not differ between groups. Also, the au-
thors reported that levels of DHEAS were significantly and
positively correlated with the intensity of aggression and
delinquency as rated by both parents and teachers. The au-
thors interpreted these results as suggesting that adrenal
androgen functioning plays an important role in the onset
and maintenance of aggression in young boys. In a second
study, van Goozen and collaborators (van Goozen, van den
Ban, et al., 2000) measured DHEAS in children with oppo-
sitional and antisocial behavior and normal controls. The
results showed that children with oppositional and anti-
social behavior had higher DHEAS levels than the control
groups. An increase in DHEAS in children and adolescents
with CD was also reported by Dmitrieva et al. (2001).
Cholesterol and Conduct Disorder
Cholesterol and, more generally, lipid concentrations and
metabolism have received substantial attention in relation
to externalizing behaviors and more specifically violence
and delinquency. Interestingly, while allostatic load in
adults and older individuals is associated with high choles-
terol levels, a negative relation is usually noted between
cholesterol and violence in both young and adults. Golomb,
Stattin, and Mednick (2000) reported that low cholesterol
levels in males were most frequently associated with violent
crimes committed against others. The participants’ age was
related to both cholesterol levels and violent crimes, but the
association remained significant when age was taken into
account. Similar results were noted in relation to physical
aggression (Hillbrand & Spitz, 1999; Hillbrand, Waite,

Miller, Spitz, & Lingswiler, 2000), past history of aggres-
sion in inpatients of a drug rehabilitation unit (Buydens-
Branchey, Branchey, Hudson, & Fergeson, 2000), violent
offenders with Antisocial Personality Disorder (Virkkunen,
1979), violent suicidal attempts (Vevera, Zukov, Morcinek,
& Papezova, 2003), and cholesterol-lowering interventions
in humans (Golomb, 1998; Muldoon, Manuck, & Matthews,
1990) and in nonhuman primates (Kaplan et al., 1994).
In contrast to the overall negative association generally
reported between cholesterol and aggression, nonsignifi-
cant or positive relationships have been noted between
cholesterol and psychological aggression, expressive hos-
tility, and anger attacks (C. C. Chen, Lu, Wu, & Chang,
2001; Hillbrand & Spitz, 1999; Wing, Matthews, Kuller,
Meilahn, & Plantinga, 1991). These results suggest that
the cholesterol and aggression association is restricted to
physical aggression and violence.
However, previous results obtained on the association
between cholesterol and CD must be accepted cautiously
for several reasons. First, most of these studies were con-
ducted exclusively with male participants, which limits the
generalization of results to females. A study conducted by
Lindberg, Rastam, Gullberg, and Eklund (1992) reported a
similar negative association between cholesterol and ag-
gression in female participants, although the magnitude of
the association was much weaker. Young age is related to
the cholesterol-aggression association, but the link remains
significant once age is taken into account, which suggests
that the association between cholesterol and aggression is
not essentially explained by the age of the child (Golomb
et al., 2000). Note that alcohol use ( linked to increased
HDL level with no change in cholesterol) and SES levels
(inversely correlated to cholesterol) do not explain the
overall relation (Golomb, 1998).
The mechanisms connecting cholesterol to physical ag-
gression are still unknown, but modified serotonin func-
tion has been proposed to mediate this association
(Buydens-Branchey et al., 2000; Mysterud & Poleszynski,
2003). Low cholesterol levels reduce lipid microviscosity in
the brain cell membrane, resulting in dampened activity in
serotonergic systems (Kaplan et al., 1994; Vevera et al.,
2003). Low serotonin levels are commonly related to a re-
duced capacity to inhibit aggressive behaviors and impul-
sivity (Coccaro, 1992; Linnoila & Virkkunen, 1992;
Virkkunen, De Jong, Bartko, & Linnoila, 1989). Cognitive
information and emotional processing are once again
thought to be implicated in the serotonin-aggression associ-
ation (Berman, Tracy, & Coccaro, 1997), namely by reduc-
ing sensitivity to external clues referring to punishment or
norm violation (Spoont, 1992).
Early Adversity and the Development of Allostatic Load 603
Other mechanisms have been shown to play a role in the
aggression-cholesterol association. Negative mood states,
low cognitive efficacy, and a reduced interpersonal in-
volvement are also linked to low cholesterol levels in an in-
patient sample (Hillbrand et al., 2000). These results
suggest that the association between aggression and choles-
terol may partially be accounted for by other psychological
and behavioral correlates.
Waist-Hip Ratio and Conduct Disorder
Very few studies have assessed the link between waist-hip
ratio and Conduct Disorders. In 2001, Ishikawa and collabo-
rators (Ishikawa, Raine, Lencz, Bihrle, & LaCasse, 2001)
measured height, weight, body mass index, bulk, and psy-
chosocial adversity in 44 controls and 43 adolescents and
adults with antisocial personalities. They reported that adult
antisocial individuals, regardless of age of onset, were sig-
nificantly taller and had greater body bulk than controls.
However, they also reported that although groups tended to
differ on weight, they did not differ on body mass index. In
2003, Mustillo and collaborators assessed the association
between obesity and the development of psychiatric disor-
ders in 991 children ages 9 to 16 who were evaluated annu-
ally over an 8-year period for height, weight, psychiatric
disorder, and vulnerabilities for psychiatric disorder. The re-
sults showed that of the four developmental trajectories of
obesity tested—no obesity (73%), chronic obesity (15%),
childhood obesity (5%), and adolescent obesity (7%)—only
chronic obesity was associated with Oppositional Defiant
Disorder in boys and girls and depressive disorders in boys.
Heart Rate and Conduct Disorder
Increased cardiovascular activity is a secondary outcome
in the allostatic load model, which is operationalized by
higher heart rate and blood pressure ( both systolic and di-
astolic). Cardiovascular parameters ( heart rate, blood pres-
sure, etc.) are easy, noninvasive, and inexpensive to collect.
Despite this apparent simplicity, it has to be noted that the
context in which measures of heart rate are collected (rest-
ing rate or activation /anticipation heart rate) may have a
major impact on the results obtained in a given study. This
makes results harder to interpret and requires at least some
caution. Also, very few studies have been conducted with
children showing the full spectrum of Conduct Disorder.
However, various studies have been performed on some of
the externalizing behaviors present in Conduct Disorders.
We summarize these two types of studies next.
A relationship between anger, hostility, elevated heart
rate, and blood pressure has been noted in several studies
(M. C. Davis, Matthews, & McGrath, 2000; Galovski,
604 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
Blanchard, Malta, & Freidenberg, 2003). Competition
challenge, harassment, and provocative insults are thought
to be central in the increased physiological reactivity asso-
ciated with anger (Garcia-Leon, Reyes del Paso, Robles, &
Vila, 2003). In contrast, instrumental and less emotionally
aroused antisocial behaviors are associated with lower
heart rate and have been suggested to reflect both an un-
derarousal state and fearlessness (Scarpa & Raine, 1997).
These sensation-seeking behaviors have been shown to
enhance the propensity for risk-taking behaviors (e.g., al-
cohol and drugs, sexual promiscuity, extreme sports), phys-
ical aggression, and criminal activities (Raine, Venables, &
Williams, 1995; Scarpa & Ollendick, 2003).
A meta-analysis conducted by Ortiz and Raine (2004) of
40 studies indicated that both resting heart rate (n = 5,868
with a mean age of 10.8 years) and reactive heart rate (n =
578 with a mean age of 12.6 years) were negatively related
to antisocial behaviors. In their prospective study, Raine,
Venables, and Mednick (1997) have reported that a low
resting heart rate assessed at age 3 in 1,795 children was
associated with higher rates of physical behaviors at age 11.
Low resting heart rates have also been linked with fighting
behaviors at age 9 to 12 years in children from low SES
(Kindlon et al., 1995). This association is still significant
when body size and pubertal status are taken into account.
Interestingly, it has been shown that stressful charac-
teristics of inner-city environments, compared to subur-
ban and rural area lifestyles and environments, are
generally linked to higher blood pressure (Thomas &
Groer, 1986). For some children, these adverse environ-
mental conditions may sensitize them to further threats,
contributing to increasing or maintaining higher resting
heart rates. However, other children confronted with the
same adverse conditions may be desensitized ( habitua-
tion) to threatening events encountered on a daily basis.
Convergent with this hypothesis, Cooley-Quille and Lo-
rion (1999) reported that youths exposed to the highest
levels of community violence have the lowest resting heat
rate. Such physiological adaptation may be protective in
the short run by dampening physiological activation asso-
ciated with stressful environments, but it can become
detrimental in the long run, placing these children at risk
to engage in developmental trajectories characterized by
externalizing problems such as delinquency and violence.
A second hypothesis for these discrepant results is that
lower heart rates in aggressive and violent individuals may
partially be explained through inherited differences in car-
diovascular activity. Moderate to strong heritability esti-
mates in cardiovascular indices are noted in several studies
in infancy (Dubreuil et al., 2003; Healy, 1992), childhood
(Boomsma & Plomin, 1986; Schieken et al., 1989), and
adulthood (An et al., 2000; Ditto, 1993; Somes, Harsh-
field, Alpert, Goble, & Schieken, 1995). Inherited differ-
ences in heart rate may enhance the propensity of
individuals with lower heart rate to manifest externalizing
behaviors while protecting individuals with higher heart
rate from personal involvement in contexts where external-
izing behaviors are adaptive or required (Kindlon et al.,
1995; Raine et al., 1995). These working models appear at
first sight hard to reconcile. Yet, although distinct, they
are not mutually exclusive. From a developmental perspec-
tive, potential factors linked to the onset of externalizing
problems are generally thought to be multidimensional
and influenced simultaneously by genes and environment
throughout one’s lifetime.
Immune Function and Conduct Disorder
To this day, only one study has assessed the unique influence
of Conduct Disorder on immune function. Birmaher et al.
(1994) assessed total white blood cells, lymphocytes sub-
sets, natural killer cell activity, and lymphocyte prolifera-
tion in adolescents with either Major Depressive Disorder or
Conduct Disorder and normal adolescents. They reported
that although there were no significant between-group dif-
ferences in any of the cellular immune measurements,
natural killer cell activity was significantly negatively cor-
related with past year and lifetime adverse life events across
all effector-target cell ratios. This result remained signifi-
cant after controlling for diagnoses and SES.
Allostatic Load and Conduct Disorder
Although the studies performed on the primary stress me-
diators and secondary outcomes of allostatic load have
shown some associations with Conduct Disorders, it is im-
portant to remind the reader that the studies that validated
the allostatic load model clearly showed that none of the
components of allostatic load exhibited significant associa-
tions on their own with health outcome. Indeed, it was
shown that it is the summary measure of allostatic load that
is significantly associated with major health outcomes.
These findings were consistent with the idea that although
a modest deviation in the level of activity of a single physi-
ologic system may not be predictive of poor future health,
the cumulative toll from modest alterations in several
physiologic systems is prognostic for poor health. Conse-
quently, it may be possible that some of the discrepant find-
ings related to primary stress mediators and/or secondary
outcomes and CD may be due to the fact that only one com-

ponent of the allostatic load model has been assessed. Al-
though no study has assessed all components of the allosta-
tic load model in children with Conduct Disorders, recent
studies measured two or more markers of allostatic load,
and the results reveal a very interesting pattern of develop-
mental allostatic load in childhood Conduct Disorders. We
summarize these next.
Low Cortisol and High Sulfated Dehydroepiandros-
terone in Conduct Disorder. As we have summarized,
independent studies have reported low cortisol levels and
high DHEAS in children with Conduct Disorders. This is
an interesting finding because the opposite pattern is ob-
served in depressed children ages 8 to 16 years, namely,
high levels of cortisol and low levels of DHEA / DHEAS
(Goodyer et al., 1996). A recent study performed in 2004
by Buydens-Branchey and Branchey assessed levels of cor-
tisol and DHEAS in 40 adult cocaine addicts with a retro-
spective diagnosis of Antisocial Personality Disorder or
childhood CD. Given that DHEAS and cortisol were as-
sessed in blood taken with venipuncture, the authors attrib-
uted any group differences in DHEAS and/or cortisol to a
difference in reactivity to the stress induced by the
venipuncture. The results showed that the men who had a
retrospective diagnosis of CD had significantly increased
DHEAS levels and less cortisol in response to venipunc-
ture. Comparisons between patients who did and did not
meet the APD adult criteria did not reveal any significant
difference in DHEAS or in cortisol responsivity.
Low Cortisol and Low Heart Rate in Conduct Disor-
der. Again, low cortisol levels and lower heart rate have
been reported in children with Conduct Disorders, but very
few studies measured these two markers at the same time
in children with Conduct Disorder. In 2000, van Goozen
and collaborators (van Goozen, Matthys, Cohen-Kettenis,
Buitelaar, & van Engeland, 2000) investigated whether a
pattern of lower autonomic nervous system and HPA axis
activity can be found in children with disruptive behavior
disorders under nonstressful and stressful conditions. They
also assessed whether the pattern of hormonal responses to
stress would correspond with the child’s feelings of control
and negative emotionality. In this study, they assessed cor-
tisol levels, heart rate, skin conductance levels, and subjec-
tive feelings of control and negative emotionality in 26
children with disruptive behavior disorder and 26 control
children. The results showed that in the baseline, nonstress-
ful condition, heart rate and skin conductance levels were
lower in children with CD, although cortisol levels were
Early Adversity and the Development of Allostatic Load 605
similar in all groups. When exposed to a stressful situation,
children with disruptive behavior disorders presented a
lower increase in heart rate and cortisol, when compared to
children without disruptive behavior disorder, but they re-
ported higher levels of emotional arousal.
In a more recent study, Snoek and collaborators (Snoek,
Van Goozen, Matthys, Buitelaar, & van Engeland, 2004)
assessed heart rate and cortisol levels in children with
Oppositional Defiant Disorder (ODD) and children with
Attention-Deficit /Hyperactivity Disorder (ADHD) under
baseline and stressful conditions. The results showed that
under baseline conditions, the groups did not differ for cor-
tisol levels, although the group of children with ODD pre-
sented lower heart rates than the ADHD group. The results
also showed that in response to stress, children with ODD
presented weaker cortisol and heart rate responses to stress
when compared to children with ADHD and control chil-
dren. Altogether, these results suggest the presence of a
hyporeactivity of the primary stress mediators (cortisol
and catecholamines/ heart rate) in response to stress in
children with ODD.
Cortisol and Immune Function in Conduct Disorder.
In the immune system, white blood cells called lympho-
cytes are very diverse in their functions. The most abun-
dant lymphocytes are the B lymphocytes (B cells) and the
T lymphocytes (T cells). The B cells are designated as such
because they are produced and mature in the Bone marrow,
and T cells are designated as such because their precursors
leave the bone marrow and mature in the Thymus. Chief
among the regulatory T cells are helper/inducer T cells.
These cells are needed to activate many immune cells, in-
cluding B cells and other T cells. Another subset of regula-
tory T cells acts to turn off or suppress immune cells.
There are two types of helper T cells. The Th1 type partic-
ipates in cell-mediated immunity and are essential for con-
trolling intracellular pathogens such as viruses and certain
bacteria. The Th2 type provides help for B cells and, in so
doing, are essential for antibody-mediated immunity. Anti-
bodies are needed to control extracellular pathogens which,
unlike intracellular parasites, are exposed to antibodies in
blood and other fluids.
Glucocorticoids have been shown to regulate the expres-
sion of Th1 and Th2 (Chrousos & Elenkov, 2000; Elenkov
et al., 2000; Elenkov, Papanicolaou, Wilder, & Chrousos,
1996; Milburn, Poulter, Dilmec, Cochrane, & Kemeny,
1997). High levels of glucocorticoids have been shown to
suppress Th1 and favor the expression of a Th2 response (a
Th2 shift), whereas decreased concentrations of cortisol
606 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
produce a shift toward Th1 function and suppress Th2 (a
Th1 shift; Chrousos & Elenkov, 2000; Elenkov et al.,
2000). This is an interesting finding because Th2 shifts are
associated with susceptibility to infections from most
types of intracellular pathogens and vulnerability to cancer
(Rabin, 1999; Shurin, Lu, Kalinski, Stewart-Akers, &
Lotze, 1999; Sprietsma, 1999). In contrast, and although a
Th1 shift has been shown to confer some protection from
these problems, it has been associated with increased sus-
ceptibility to “stress-related” disorders such as fibromyal-
gia and chronic fatigue syndrome (Clauw & Chrousos,
1997; Crofford, Jacobson, & Young, 1999; Griep et al.,
1998; Lentjes, Griep, Boersma, Romijn, & de Kloet, 1997;
Scott, Medbak, & Dinan, 1998), as well as autoimmune (al-
Wabel, al-Janadi, & Raziuddin, 1993; Balomenos, Rumold,
& Theofilopoulos, 1998; Gutierrez, Garcia, Rodriguez,
Rivero, & Jacobelli, 1998), and inflammatory (Chrousos,
1995; Harbuz, Jessop, & Lightman, 1997) disease.
Given that low cortisol levels have been correlated with
a shift toward Th1 (predominance of Th1 with suppression
of Th2), Pajer and collaborators (Pajer, Rabin, & Gardner,
2002) recently conducted a study in young girls with anti-
social behavior to assess whether the low cortisol profile
generally observed in children with Conduct Disorder is
associated with a shift toward Th1. In this study, the au-
thors used plasma levels of IgG3 and IgG4 as markers for
Th1 and Th2 activity and assessed the IgG 3⬊4 ratios in 42
teenage girls with CD or controls. Results showed that the
mean IgG 3⬊4 ratio was higher in the girls with CD and
that cortisol levels were significantly and negatively corre-
lated with IgG 3⬊4 ratio. These new findings indicate that
immunologic abnormalities are present in relation to low
cortisol levels in adolescents with CD.
The various studies that have been performed in rela-
tion to hormonal and immune dysfunctions in Conduct
Disorders tend to show that lower levels of the primary
stress mediators cortisol and catecholoamines (through
cardiovascular indices) are associated with Conduct Disor-
ders and that these lower levels of activity are associated
with higher levels of DHEAS and immune changes. It is in-
teresting to note that the pattern of changes in the media-
tors of allostatic load is different from the pattern that has
been observed in older adults. Indeed, in older popula-
tions, increased levels of the primary stress mediators cor-
tisol and catecholamines and lower levels of DHEAS have
been reported to predict functional decline later in life
(Seeman, McEwen et al., 2001; Seeman et al., 1997). It is
therefore possible that the differences in allostatic stress
mediators reported to occur in children and older adults
may be due to differences in psychological characteristics
of the populations (Conduct Disorders versus normal pop-
ulations) or to significant developmental differences in the
pattern of allostatic load across the life span (younger ver-
sus older adults).
Validation of Allostatic Load in Children
A very interesting study published in 2003 by G. W. Evans
gives us very valuable data about normal childhood and al-
lostatic load. Actually, this is the only study published to
date that specifically assessed the various components of
allostatic load in a population of children. In this study,
339 low-income children with a mean age of 9 were re-
cruited from public schools in New York State. Evans eval-
uated the cumulative environmental risk factors using the
same method previously described for physical environ-
mental risk (crowding, noise, housing quality; see G. W.
Evans & Marcynyszyn, 2004). Moreover, psychological
risk factors (child separation, turmoil, violence) were also
assessed, as well as aspects of the home environment and
personal characteristics (poverty, single parenthood, ma-
ternal high school dropout). As well, two behavioral proto-
cols were included to examine self-regulatory behavior and
learned helplessness. The child’s ability to delay gratifica-
tion was used as an index of self-regulatory behavior, and
learned helplessness was evaluated with a standard behav-
ioral protocol. Finally, measures of allostatic load included
resting blood pressure (diastolic and systolic), overnight
urinary neuroendocrine measures (cortisol, epinephrine,
and norepinephrine), an index of fat deposition ( body mass
index), and a total allostatic load index (0 to 6) reflecting
the number of these six singular physiological indicators on
which each child scored in the top quartile of risk. The re-
sults of this study showed that all three primary stress
mediators (cortisol, epinephrine, norepinephrine) were ele-
vated by cumulative risk exposure and that body mass
index was significantly and positively related to cumulative
risk exposure. More important, the author reported that the
total allostatic load index was significantly related to cu-
mulative environmental risk. Interestingly, it was found
that children’s own perceptions of self-worth were unre-
lated to any allostatic load indicators but were positively
correlated with task persistence on the learned helpless-
ness puzzle. Besides being the first study specifically as-
sessing allostatic load in normally developing children, this
study is very important because it shows that in low-income
children without Conduct Disorders (although presence or
absence of Conduct Disorder was not specifically assessed
in this study), higher allostatic load scores on primary

stress mediators and secondary outcomes are observed.
This is a very interesting finding in line with previous data
summarized in children with Conduct Disorders, suggest-
ing that when behavioral problems and/or symptoms be-
come apparent in children, most markers of allostatic load
are decreased. In his study, Evans tested the presence of a
curvilinear function between cumulative environmental
risk and allostatic load score, and the quadratic function
proved to be significant. This result strongly suggests that a
mechanism of early adaptation to allostatic load may exist,
whereby the organism tries to adapt to environmental de-
mands. As we have argued in previous sections of this
chapter, this mechanism of adaptation may be closely re-
lated to the cognitive interpretation given to adverse events
in order to adapt to the various challenges of life.
However, another possibility has to be raised with regard
to the different results obtained on allostatic load in various
populations. Indeed, it is quite possible that these different
patterns of allostatic load are due to genetic influences act-
ing on the stress mediators, leading to increased risk for the
development of CD during childhood.
McEwen and Stellar (1993) have highlighted the idea
that, early in infancy, genetic predispositions and environ-
mental factors contribute to laying down the individual dif-
ferences in subjective perceptions attributed to a threat
(relevant or not) and then physiologically responding to it.
As a result of cumulative threats (or less intense experi-
ences) over time, initial differences in the response to
stressful events could be altered (either minimized or en-
hanced), resulting in vulnerability to diseases (Repetti,
Taylor, & Seeman, 2002; Rutter, 1994). To date, re-
searchers in developmental psychopathology have devoted
great effort to studying the associations and mechanisms
linking early proximal (e.g., parental behaviors, parent-
child relationships) and distal (e.g., poverty, dangerousness
of neighborhood) environmental characteristics and the in-
dividual differences of presenting pathology. Results ob-
tained from animal models (Meaney et al., 1991) and
studies conducted with humans (G. W. Evans, 2003; Felitti
et al., 1998; Gunnar et al., 2001; Hertsgaard, Gunnar, Er-
ickson, & Nachmias, 1995) show promising features in our
understanding of the trajectories leading to allostatic load.
Less is known about the potent influences that genetic fac-
tors may have on allostatic load.
Considering that allostatic load is a complex syndrome
involving several physiological mediators, regulatory sys-
tems, and stress-related structures (Repetti et al., 2002;
Seeman, McEwen et al., 2001; Seeman, Singer, Ryff, Dien-
berg Love, & Levy-Storms, 2002), the estimation of the
Early Adversity and the Development of Allostatic Load 607
overall impact of genes on allostatic load appears prema-
ture and questionable for several reasons. First, no empiri-
cal evidence allows for the assumption that individuals are
similarly characterized across primary mediators: Are in-
dividual differences in primary mediators correlated? Sec-
ond, primary mediators may have distinct trajectories
leading to diseases: Does a dysfunction of the HPA axis in-
duce a similar vulnerability for anxiety-related problems
compared to an altered catecholamine system? Third, pri-
mary mediators may show different etiological patterns:
Are primary mediators regulated by common or different
genes/environments? Are primary mediators regulated by
the same genes/environments across the life span? Current
data show that genetic influences on some phenotypes
might be enhanced during development, whereas the ge-
netic influence on other phenotypes might be “ turned on”
or “ turned off ” later in life (Plomin, DeFries, McClearn,
& McGuffin, 2001). Finally, considering that allostasis and
allostatic load are probably multifactorial (e.g., influenced
by several genes and environments), as are most complex
phenotypes, the remaining question in estimating genetic
and environmental influences on individual differences in
allostatic load should be considered cautiously. Accord-
ingly, the genetic influences on allostatic load could be
more efficiently understood through studying their impact
on more elementary neurobiological traits, such as primary
mediators (de Geus, 2002). That is, primary mediators may
be referred as endophenotypes of allostatic load, which al-
lows a more valid examination of the respective roles of
etiological factors (environments and genes) to each pri-
mary mediator (HPA axis, catecholamine, and DHEA) and
consequently to the complex construct of allostatic load.
Genetic Inf luences on the Hypothalamic-
Pituitary-Adrenal Axis: Results from Twin Studies
The HPA axis is one of the most studied primary media-
tors. Behavioral genetic analyses offer a powerful tool to
investigate the etiology of individual variations for a trait
in a population (D. M. Evans, Gillespie, & Martin, 2002).
In behavioral genetic modeling, genetic and environmental
sources of variance of a phenotype (or endophenotype) are
disentangled by using measures collected from participants
who differ in their degree of genetic relatedness (Plomin
et al., 2001). In twin studies, genetic models are based on
monozygotic (MZ; identical twins, sharing 100% of their
genes) and dizygotic (DZ; fraternal twins, sharing approxi-
mately 50% of their genes) twin intraclass correlation com-
parisons. Typically, four main sources of variance can be
608 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
assessed and generally symbolized by the following capital
letters (parameters): [A] represents the additive genetic ef-
fect (the effect of an allele is added to the effect of other
alleles); [D] the nonadditive genetic effect (resulting from
interaction between alleles at the same locus, dominance,
or at different loci, epistasis); [C] the common environment
effect, linked to the experience of similar environments
within twin pairs; and [E] the unique environment effect,
which also includes the measurement errors (Posthuma
et al., 2000). In short, twin design studies allows us to esti-
mate the magnitude of the genetic and environmental ef-
fects on a phenotype, and the mode of transmission (i.e.,
additive or nonadditive) that best reflects genetic covaria-
tion between participants (for extended description of ge-
netic modeling in twin design studies, see D. M. Evans
et al., 2002; Neale & Cardon, 1992; Posthuma et al., 2000).
We highlight some empirical results of heritability re-
ported from twin studies about individual differences in
HPA axis (re)activity, underlining the main limitations
and interpretations from a heuristic and methodological
standpoint, and identifying future areas that will need to be
investigated to initiate a comprehensive conceptual frame-
work of modulatory influences of genes to allostatic load
and psychopathology.
Large individual variations are noted in HPA axis
(re)activity (Wüst et al., 2000). Genetic factors are thought
to play an important role in the individual differences in
HPA axis (re)activity. Surprisingly few studies have at-
tempted to estimate the heritability of cortisol levels, al-
though twin designs offer a great opportunity to assess
genetic and environmental influences. Concerning nonre-
active cortisol levels, reported heritability estimates vary
considerably from one study to another, ranging from 0 to
74% (for a review, see Bartels, Van den Berg, Sluyter,
Boomsma, & de Geus, 2003). Wüst and his colleagues have
collected saliva samples after awakening on two consecu-
tive days from 52 MZ and 52 DZ twin pairs ages 8 to 65
years old. They observed moderate genetic effects on
saliva cortisol levels for the main increase in awakening
cortisol response ( h2 = .40) and for the area under the
curve ( h2 = .48). This finding is consistent with that of
Kirschbaum and collaborators (Kirschbaum, Wüst, Faig, &
Hellhammer, 1992), who reported a significant influence of
genetic factors on the three baseline measures of salivary
cortisol levels collected before stimulation procedures
(CRH test, ergometry, and public speech). Meikle, String-
ham, Woodward, and Bishop (1988) obtained similar heri-
tability estimates with plasma cortisol levels ( h2 = .45 for
total cortisol and h2 = .51 for unbound cortisol) in 20 MZ
and 20 DZ twin male pairs. Bartels, de Geus, Kirschbaum,
Sluyter, and Boomsma (2003) recently reported significant
heritability estimates on cortisol levels sampled at several
times on two consecutive days in 12-year-old twin pairs (n
= 180). Results showed higher cortisol heritability esti-
mates for samples collected 45 minutes after awakening ( h2
= .60), moderate estimates around noon ( h2 = .30), and null
estimates in the evening. Other results also suggest moder-
ate genetic influences for nonreactive cortisol levels (Inglis
et al., 1999; Young, Aggen, Prescott, & Kendler, 2000). In
spite of these results, other studies report null heritability
estimates for basal cortisol levels (Froehlich, Zink, Li, &
Christian, 2000; Meikle et al., 1988; Pritchard et al., 1998).
Furthermore, some empirical results showed that the day-
time cortisol profile is moderately influenced by shared en-
vironments (Wüst et al., 2000), although this finding
appears inconsistent (Linkowski et al., 1993).
Heritability estimates of reactive cortisol levels (in re-
sponse to stress) lead to divergent results, although
most of them suggest no or minor genetic effects in corti-
sol responses to various stressful events or tasks (Nurn-
berger et al., 1982; Pritchard et al., 1998). For example,
Kirschbaum et al. (1992) found no significant intraclass
correlation differences between MZ and DZ twin pairs’
cortisol levels in response to physical and psychological
stress paradigms. In contrast, they obtained significant
intraclass correlation differences during the administra-
tion of corticotropin-releasing factor (CRF; stimulates the
HPA axis), suggesting that HPA axis responses to CRF
may be influenced by genes via negative feedback retroac-
tion loops. In these studies, no significant estimate of
common environmental factors was reported.
Disparities noted for heritability estimates may be ac-
counted for by various methodological procedures, such as
collection methods (plasma, salivary, and urine samples),
time of collection (at waking, before bedtime, before or
after a stressful activity), and small sample size (Bartels,
Van den Berg et al., 2003). Time of sampling and the nature
of sampling (reactive or not) are particularly important as
we are still unsure whether different genes may influence
cortisol levels at different times of the day and what may be
the common or different etiological factors related to non-
reactive and reactive cortisol levels. Recent results suggest
that estimates of genetic and environmental variance com-
ponents vary sufficiently across the day to induce distinct
etiological patterns of cortisol secretion at different times
of the day (Bartels, de Geus et al., 2003). Why there are
differences in genetic and environmental estimates in cor-
tisol levels sampled at distinct times of the day is still
unknown. Small sample size is another issue that could par-
tially explain discrepancies between reported heritability

estimates. Most of these studies do not allow sufficient sta-
tistical power to distinguish the variance related to genes
from the variance associated with common environments
(Bartels, Van den Berg et al., 2003). As a result, genetic,
common, and unique environment variance components are
estimated, more often than not, through MZ and DZ intra-
class correlations (except Bartels, de Geus et al., 2003;
Bartels, Van den Berg et al., 2003). The main limitation of
estimating heritability through rough comparisons of intra-
class correlation is that it does not take into account the
dispersion indices related to the evaluated phenotype.
Moreover, this statistical procedure does not allow us to es-
timate confidence intervals and does not provide any statis-
tical parameters that specify how well the chosen model
(rather than other tested models) best describes the ob-
served data (Posthuma et al., 2000).
To overcome these limitations, Bartels and her col-
leagues (Bartels, Van den Berg et al., 2003) have performed
a simultaneous analysis by using structural equation mod-
eling to fit data collected in five distinct studies selected
on the basis of similar methodological characteristics
(Froehlich et al., 2000; Inglis et al., 1999; Linkowski et al.,
1993; Meikle et al., 1988; Wüst et al., 2000). A heritability
estimate of 62% was obtained for nonreactive cortisol lev-
els, suggesting that over half of the individual differences
observed in basal cortisol levels can be attributed to addi-
tive genetic factors. The most parsimonious model includes
no parameter for common environment. The remaining
variance (38%) was attributed to uniquely experienced en-
vironment (i.e., environmental factors affecting the chil-
dren within the twin pair differently). This result points to
a moderate genetic component of basal cortisol levels
across a large age span (i.e., 8 to 67 years old).
Theoretical Implications and Misleading
Interpretations of Twin Studies’ Results
No inf luence of the twins’ shared environments on the HPA
axis? In light of the results emerging from twin studies, one
might be tempted to conclude that common environmental
factors do not exert a significant influence on individual
differences in nonreactive cortisol secretion. These find-
ings are surprising given the fact that other studies have re-
ported that adverse environments, including poverty, low
parental education attainment, placement in orphanage,
and parental negative behaviors, have a detrimental effect
on cortisol levels and circadian rhythms (Flinn & England,
1997; Gunnar et al., 2001; Lupien et al., 2000; Taylor,
Repetti, & Seeman, 1997). Can we reconcile these diver-
gent conclusions? One interpretation may reside in distin-
guishing the characteristics of those studies from the twin
Early Adversity and the Development of Allostatic Load 609
studies’ samples. Bear in mind that environmental and ge-
netic estimates can be interpreted only in the population
from whom data have been collected (Plomin et al., 2001).
No generalization of the results can be drawn to other pop-
ulations. The majority of the heritability estimates re-
ported in twin studies are issued from normative samples
of twins mostly not confronted with intense and chronic
stressful environments. Accordingly, the reported heri-
tability estimates should not be extended or compared to
clinical samples, which are particularly at risk in light of
highly adverse environments, mainly because it is still un-
known if there are relevant differences in genetic and envi-
ronmental estimates that result from normative samples in
comparison to clinical samples.
Another interpretation of the nonsignificant shared
environmental factors reported by twin studies refers to dif-
ferent processes by which environmental factors may influ-
ence the HPA axis (re)activity at different periods of
development. Infancy has long been conceived as a sensitive
period of development mostly because several physiological
systems have not completed their maturational processes
and thus show considerable plasticity to environmental con-
ditions (Andersen, 2003; De Kloet et al., 1998). Prenatal
and early environments have been suggested to have impor-
tant organizational and stable effects on primary mediators
and, to a greater extent, on several regulatory systems, in-
cluding the stress-related system (e.g., hippocampus,
amygdala, hypothalamus; Repetti et al., 2002; Weinstock,
1997). Increased sensitivity to environmental conditions
may allow the organism to achieve short-term or long-term
adaptations to this environment (Huether, 1998; Teicher
et al., 2003). However, the cost of stable modifications in
stress-related systems, as induced by environmental factors
experienced during the sensitive period, may not always be
optimal, sometimes placing the organism in a long-standing
allostatic load (McEwen, 2003).
Although the mechanisms associated with the perma-
nent effects of early environments on individual differ-
ences in HPA axis (re)activity have not been fully
understood, the role of glucocorticoid receptors is high-
lighted (Blackhurst et al., 2002; Takahashi, 1998; Welberg
& Seckl, 2001). In rodents, postnatal handling during the
1st week of life has been shown to decrease stress reactiv-
ity later in life, perhaps through alterations in CRF gene
expression in the paraventricular nucleus of the hypothala-
mus and the amygdala, resulting in increased glucocorti-
coid negative feedback via the glucocorticoid receptors
(Meaney, 2001; Plotsky & Meaney, 1993; Vallee et al.,
1997). In contrast, maternal separation occurring early in
life induces increased HPA axis responses to stress that are
610 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
sustained in adulthood (Plotsky & Meaney, 1993). Alter-
ations in CRF gene expression may contribute to this asso-
ciation. The effects in HPA axis regulation through
manipulations of the pups’ early proximal environments
have been closely related to the overall modifications in
time and/or quality of maternal care of the offspring
(Champagne, Francis, Mar, & Meaney, 2003). Further-
more, mothers’ individual differences in maternal care
have been reported to have a nongenomic effect on HPA
axis regulatory functions of their offspring, rather than in-
herited common genes related to the phenotype character-
izing reactivity to stress (Francis, Champagne, Liu, &
Meaney, 1999; Francis, Diorio, Liu, & Meaney, 1999). In
other words, pups’ individual differences in (re)activity
are suggested to be genetically encrypted in their geno-
type, not through inherited characteristics but through epi-
genetic programming induced by maternal care (Weaver
et al., 2004).
Can the results indicating an important influence of
early environments to later HPA axis (re)activity be recon-
ciled with those from twin studies indicating nonsignifi-
cant contributions of shared environmental factors? Note
that the estimations of shared environmental factors’ influ-
ence in twin studies are exclusively conducted from late in
childhood to old age, thus, after the sensitive period high-
lighted in the studies that show considerable organizational
effects of early environment to HPA axis (re)activity. This
could explain, at least in part, some inconsistencies. Fur-
thermore, bear in mind that behavioral genetic modeling
estimating the sources of variance related to genetic and
environmental factors in individual differences in HPA axis
(re)activity are conducted without any specific considera-
tion for the organizational effects of environments experi-
enced during the sensitive period. To what extent those
environments increase or decrease similarities within MZ
and DZ twin pairs is therefore unknown. Taken together,
these considerations underline the importance of adopting
a prospective view of genetic and environmental influences
in individual differences on HPA axis (re)activity. A closer
examination of etiological sources of variance in individual
differences in HPA axis (re)activity in infancy is then
strongly needed because other mechanisms may be associ-
ated with individual differences in HPA axis throughout
development.
Gene-Environment Interactions. Early environ-
ments have been shown to have organizational and long-
standing influences in shaping individual differences in
HPA axis (re)activity, particularly during the sensitive pe-
riod in infancy. After this period, individual differences in
HPA axis (re)activity from both inherited and early envi-
ronmentally settled genetic factors are suggested to inter-
act with incoming environmental factors to determine
the larger observed individual differences in HPA axis
(re)activity (Anisman, Zaharia, Meaney, & Merali, 1998;
McEwen, 2000a; Repetti et al., 2002). Interaction between
genes and the environment refers to the idea that genetic
factors influence the sensitivity of a given phenotype to
distinct environmental settings (Rutter & Silberg, 2002).
For example, a child who inherits a phenotype linked to
high reactive responses to stress may be more vulnerable
when confronted with more adverse stressful environments
(e.g., environments exacerbate his or her genotype) relative
to environments that do not present any significant stress
factors. Bronfenbrenner and Ceci (1994) have gone beyond
this assertion to specify that when synergistic effects re-
sulting from genetic-environment interactions are weak,
genetic potentials related to the phenotype (e.g., genotype)
remain relatively unrealized. However, the potential should
be progressively more actualized when gene-environment
interactions become more stringent, specifically referring
to more adverse stressful environments in association with
HPA axis (re)activity. No twin studies have tested models
including a parameter for the gene-environment interac-
tions. In the context of significant genetic-environment in-
teractions, the variance associated with the interaction
factor is relegated to the genetic component, resulting in
spurious inflated estimations of the genetic parameters and
misleading interpretations about shared environment con-
tributions. Further studies should address the conceptual
and prospective processes related to individual differences
in HPA axis (re)activity.
Unique Environments. According to the reported
studies, a significant proportion of the total individual
variance in the HPA axis (re)activity is consistently attrib-
uted to the unique environment parameters (Wüst et al.,
2000). Unique environment components include, in addi-
tion to all measurement errors (e.g., sampling procedures
and collecting time), environmental factors not shared
within twin pairs. Nonshared environmental factors in-
volved in the unique environment’s estimate are theoreti-
cally unlimited, varying from different classes at school
and distinct significant friends to more complex factors
that constitute the cognitive processing of information.
Confronted by similar threatening contexts, individuals
may show different physiological responses according to
the unique cognitive schemas activated and to the per-

ceived coping response availability and efficiency. Those
nonshared environments contribute to increasing the non-
shared source of variance estimated. However, these non-
shared environmental factors may represent promising
areas of interventions (e.g., cognitive therapy).
FUTURE DIRECTIONS
Based on our review of the model of allostatic load and our
description of the potential effects of allostatic load on
child development as a function of early adversity, we be-
lieve that there are two major issues that should be investi-
gated in the next decade. The first relates to the importance
of taking into consideration the hormonal milieu of the
mother ( both pre- and postnatally) when studying stress re-
activity and allostatic load in children. The second relates
to the importance of considering how early adversities can
impact the developing brain and lead to increased reactiv-
ity to stress and/or trauma in adulthood.
The Hormonal Milieu of the Mother in the
Prenatal and Postnatal Periods
Pregnancy is associated with major changes in hormone
levels, and the post-partum period that follows birth is also
associated with drastic modifications of hormone levels.
Recent studies performed in both animals and humans sug-
gest that the hormonal milieu of the mother in the prenatal
and postnatal period might have significant impact on the
child’s development.
Prenatal Period
A growing body of empirical evidence, based on method-
ologically rigorous studies of pregnant women of different
ethnic, socioeconomic, and cultural backgrounds, supports
the premise that mothers experiencing high levels of psy-
chological or social stress during pregnancy are at signifi-
cantly increased risk for preterm birth or low birthweight
(Hedegaard, Henriksen, Sabroe, & Secher, 1993; McLean
et al., 1995; Paarlberg, Vingerhoets, Passchier, Dekker, &
Van Geijn, 1995; Rini, Dunkel-Schetter, Wadhwa, & Sand-
man, 1999; Wadhwa, Sandman, Porto, Dunkel-Schetter, &
Garite, 1993). Recent epidemiological studies in Europe,
North America, and the developing world suggest that ba-
bies born at term with low weight (intrauterine growth re-
tardation; IUGR) will develop with high prevalence several
pathologies, including insulin resistance, Type 2 diabetes,
hypertension, and ischemic heart disease, during adult life
Future Directions 611
(Barker et al., 1993; Phillips, 1998). It is interesting to note
that the physiological disorders observed in low birth-
weight babies have all been associated with secondary
outcomes of allostatic load in adult life (see earlier discus-
sion). Such an association between IUGR and the appear-
ance of diseases in later life has led to the fetal origin
hypothesis (Barker et al., 1993), which suggests that ad-
verse environmental factors acting in utero program the de-
velopment of fetal tissues, producing later dysfunctions
and diseases.
The effect sizes of maternal stress on birthweight in
well-controlled prospective studies with large sample sizes
(more than 1,000 women) have typically ranged between
1.5-fold and 2-fold increase (Hedegaard et al., 1993; Hede-
gaard, Henriksen, Sabroe, & Secher, 1996; Peacock, Bland,
& Anderson, 1995). Most of these studies have shown that
within the range of stressors that are related to low birth-
weight, the time of exposure to the stressor is the important
variable. Chronic exposure to stress in the pregnant
mother, more than exposure to acute stress per se, is the
most important variable related to low birthweight in the
child (Hedegaard et al., 1993; McLean et al., 1995; Paarl-
berg et al., 1995; Rini et al., 1999; Wadhwa et al., 1993). A
human study performed by Wadhwa and collaborators
found that, independent of biomedical risk, each unit in-
crease of prenatal life event stress (from a possible sample
range of 14.7 units) was associated with a 55.03 g decrease
in infant birthweight and a significant increase in the likeli-
hood of low birthweight (odds ratio = 1.32).
Programming is related to a specific time window dur-
ing development and persists during the whole life span
(Seckl, Cleasby, & Nyirenda, 2000). One reason the pro-
gramming effects of prenatal environmental stress are per-
manent is assumed to be due to enduring effects on the HPA
axis (Ader, 1969; De Kloet et al., 1998; Meaney, 2001;
Meaney, Aitken, Viau, Sharma, & Sarrieau, 1989; Meaney
et al., 1996; Menard, Champagne, & Meaney, 2004; Plotsky
& Meaney, 1993; Weaver et al., 2004; Weinstock, 1997)
and the resulting high secretion of glucocorticoids. Re-
cently, it has been shown that these changes in program-
ming are linked to alterations in glucocorticoid receptors in
the limbic system (Lesage, Blondeau, Grino, Breant, &
Dupouy, 2001; Levitt, Lindsay, Holmes, & Seckl, 1996;
Lingas, Dean, & Matthews, 1999). Because the hippocam-
pus contains high levels of glucocorticoid receptors and is
an important regulator of glucocorticoid negative feedback
(De Kloet et al., 1998; Jacobson & Sapolsky, 1991), it has
been assumed that changes in receptor expression will po-
tentially alter negative feedback thresholds within the HPA
612 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
axis, leading to chronically high levels of glucocorticoids in
prenatally stressed individuals, which could in turn impact
cognitive development in the child.
Indeed, rats exposed in utero to high levels of glucocor-
ticoids have been shown to present significant memory
impairments when compared to rats not exposed to stress
in utero (Lemaire, Koehl, Le Moal, & Abrous, 2000; Szu-
ran, Pliska, Pokorny, & Welzl, 2000; Welberg & Seckl,
2001). In humans, studies reveal an association between
prenatal glucocorticoid overexposure and impaired cogni-
tive development (for a review, see Buitelaar, Huizink,
Mulder, de Medina, & Visser, 2003) and between stress
during pregnancy and general cognitive development and
language functioning in toddlers (Laplante et al., 2004).
Both prematurity and IUGR are consistently associated
with cognitive impairments (Buitelaar et al., 2003). Other
data suggest that cognitive outcomes are more seriously
compromised by growth restriction than by prematurity
(Lagercrantz, 1997). Earlier studies, using more global
measures of cognitive development, such as IQ tests, re-
ported significant impairments among IUGR children
(Breslau, Chilcoat, DelDotto, Andreski, & Brown, 1996;
Hutton, Pharoah, Cooke, & Stevenson, 1997; Landry,
Smith, Miller-Loncar, & Swank, 1997; Martyn, Gale,
Sayer, & Fall, 1996; Seidman et al., 1992). As adults,
IUGR babies are less likely to hold managerial /profes-
sional employment and earn less income (Strauss, 2000),
suggesting that growth-related impairments in cognitive
development are functionally relevant.
Altogether, these findings provide a strong set of data
suggesting that exposure to stress in pregnancy might have
a profound influence on birthweight and postnatal cogni-
tive development, and consequently, that one could use an
individual’s birthweight /gestational age as a good proxy
for exposure to prenatal early adversity. Future studies as-
sessing the effects of maternal stress during pregnancy and
reactivity to stress and cognitive function in the children
should provide very valuable data on the effects of prenatal
exposure to stress on allostatic load later in life.
Postnatal Period
Giving birth and caring for a newborn is a highly emotional
and stressful experience for a new mother. Across all
species, physiological and behavioral changes prepare the
mother for the arrival of her offspring. In the past few
decades, animal studies have documented considerable
plasticity in the maternal brain during pregnancy and lac-
tation (for a review, see Russell, Douglas, & Ingram,
2001). These changes, which span late gestation through-
out lactation, ensure optimal infant development through
the establishment of maternal behavior (animal’s nest
building, retrieval, licking and grooming; reviewed by
Numan, 1994), metabolic resetting, and neuroendocrine
changes. During human pregnancy and the transition to
lactation, major hormonal changes occur within a short pe-
riod of time. Maternal levels of estrogens and progesterone,
which increase gradually during pregnancy (about 10- to
20-fold for progesterone and 100-fold for estradiol concen-
trations), suddenly drop at delivery and return to pregravid
levels within a few days. Just as in any other mammalian
species, human maternal behavior and changes in mood,
emotion, and cognition are then initiated in the preparation
for motherhood (Russell et al., 2001).
Feeding Choice
It is interesting to note that earlier studies conducted in ro-
dents have demonstrated that lactation is associated with a
period of hyporesponsiveness to various stressors in moth-
ers (Carter & Lightman, 1987; Higuchi, Honda, Takano, &
Negoro, 1988; I. D. Neumann et al., 1998; Toufexis et al.,
1998). More important, it has been shown that this period
of stress hyporesponsiveness in mothers is associated with
the same stress hyporesponsiveness period in pups (Dent,
Smith, & Levine, 2000; Levine, 1994; Schapiro, Geller, &
Eiduson, 1962). The main characteristics of this period in
pups are very low basal glucocorticoid levels and an inabil-
ity of many stressors to elicit a glucocorticoid response
(Levine, 1994).
The presence of a stress hyporesponsiveness period in
the mother is related to lactation (Hard & Hansen, 1985;
Hary, Dupouy, & Chatelain, 1981; Lightman & Young,
1989; I. D. Neumann, Toschi, Ohl, Torner, & Kromer, 2001;
Shanks et al., 1999; Stern, Goldman, & Levine, 1973;
Walker, Lightman, Steele, & Dallman, 1992; Walker, Trot-
tier, Rochford, & Lavallee, 1995; Windle, Brady, et al.,
1997; Windle, Wood, et al., 1997; Witek-Janusek, 1988)
and to the role of central oxytocin and prolactin release in
discrete regions of the hypothalamus throughout lactation
(for a review, see Torner & Neumann, 2002; Torner, Toschi,
Nava, Clapp, & Neumann, 2002). Oxytocin and prolactin,
respectively involved in milk ejection and production, not
only have known anxiolytic effects in both male and female
virgin rats, but also play an important role in the onset of
maternal behavior (Bridges, 1984; Bridges, Numan, Ron-
sheim, Mann, & Lupini, 1990; Carter & Lightman, 1987;
Higuchi et al., 1988; I. D. Neumann, Russell, & Landgraf,
1993; I. D. Neumann et al., 2001; Torner et al., 2002).
Humans differ from animals in their choice to breast-
feed or not. In contrast to bottle-feeding, breast-feeding
will initiate the hormonal response of oxytocin and pro-

lactin, which have been shown to be involved in the stress
hyporesponsive period. Consequently, women who breast-
feed may present a hyporesponsive response to stress when
compared to women who bottle-feed. Such a result has
been obtained in human mothers. For example, Wiesenfeld
and collaborators (Wiesenfeld, Malatesta, Whitman,
Granrose, & Uili, 1985) first showed that breast-feeding
women exposed to infant signals display blunted autonomic
skin conductance responses, compared to bottle-feeding
mothers. Along with these findings, about a decade later, it
was shown that, at 8 to 18 weeks postpartum, breast-feed-
ing mothers have blunted HPA axis responses to a stressful
treadmill exercise, compared to bottle-feeding mothers
(Altemus, Deuster, Galliven, Carter, & Gold, 1995). These
findings seem to suggest that women who breast-feed have
blunted physiological responses to potentially stressful
events. This could differentially impact reactivity to stress
directly relevant to the infant and/or impact the child’s hy-
poresponsivity to stress as well.
Consequently, it could be proposed that by inducing
stress hyporesponsivity to environmental stressors, breast-
feeding could serve as a protective factor for the mother
(and possibly for her child) from repeated and/or excessive
secretion of plasma and milk glucocorticoids during the
postpartum period (Patacchioli et al., 1992; Yeh, 1984). In
contrast, by preventing the emergence of the naturally oc-
curring hyporesponse to neutral stressors, bottle-feeding
might enhance the woman’s reactivity to stressors and thus
lead to repeated and/or excessive secretion of glucocorti-
coids. As we have summarized in this review, excessive se-
cretion of cortisol levels in humans has been associated
with memory impairments (Lupien et al., 1997, 2005;
Lupien & Lepage, 2001; Lupien & McEwen, 1997; Maheu
et al., 2004) and emotional disturbances (Sachar et al.,
1973). Interestingly, a study published in 1992 reported a
significant negative correlation between glucocorticoid
levels and the mood of mothers who bottle-fed their babies
(Bonnin, 1992). Breast-feeding is certainly not the only
protective factor during this critical period, but as one that
is easily accessible to all mothers, it might be one that
could be strongly encouraged in specific populations ex-
posed to high levels of environmental stress (i.e., low SES
communities). These populations also choose more fre-
quently not to breast-feed. It is thus possible that some of
the effects of early adversities that are shown in children’s
development are due to the hormonal milieu of mothers at
the time of birth of the child, induced by the feeding mode
chosen by mothers. Clearly, further studies assessing the
impact of infant feeding choice on the child’s behavior are
needed to elucidate this intriguing association between in-
Future Directions 613
fant feeding mode and stress reactivity in both the mother
and her child.
Parity
Studies investigating stress responses have concentrated
mostly on primiparous mothers, as the most dramatic
changes in lifestyle occur after the first childbirth. Being a
mother for the first time can at times be an emotionally in-
tense and stressful experience in a woman’s life. Even
though fatigue and sleep disruption in maternal role “ac-
quisition” in primiparous mothers is comparable to those
experiences associated with the role of “expansion” in
multiparous mothers (Waters & Lee, 1996), women with
prior childbirth experience are less anxious and depressed
(Fleming, Ruble, Krieger, & Wong, 1997; Fleming, Steiner,
& Corter, 1997), undergo shorter and less painful labor
(Mahon, Chazotte, & Cohen, 1994), and are less likely to
experience gestational complications (Da Costa, Larouche,
Dritsa, & Brender, 2000) and delayed lactogenesis in the
days following delivery (D. C. Chen, Nommsen-Rivers,
Dewey, & Lonnerdal, 1998), compared to primiparous
mothers. In fact, parity is inversely correlated with the
amount of life change (Grace, 1993). Thus, it is not surpris-
ing that multiparous mothers also display lower glucocorti-
coid levels during the days following delivery (Grajeda &
Perez-Escamilla, 2002) and have more positive maternal
attitudes and attractiveness to infant odors (Fleming,
Steiner, et al., 1997). However, currently no study has in-
vestigated the changes in stress responsiveness as a func-
tion of parity. Future studies assessing stress reactivity in
both mothers and children as a function of parity could
lead to very interesting results.
Indeed, a few studies in the animal literature have inves-
tigated “ habituation” of neuronal functions with respect to
parity. This habituation process might also be present in
the human population. Boukydis and Burgess (1982) ob-
served higher arousal to infant cries in first-time mothers
compared to mothers with several children and nonparents.
This parity-induced attenuation in responsiveness is not
surprising considering the fact that with repetitive expo-
sure, the novelty characteristic of a stressful or emotional
event is lost as the subject gains experience. This, in turn,
can alter stress appraisal to the benefit of the mother, so
that responsiveness to stress should be high only in situa-
tions of actual child endangerment. On the other hand,
multiple demands placed on multiparous mothers increase
fatigue (Sammons, 1990), which could enhance vulnerabil-
ity to external stressors and lead to increased risk for post-
partum depression (Righetti-Veltema, Conne-Perreard,
Bousquet, & Manzano, 1998). Even though parity does not
614 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
play a significant role in occupational fatigue in working
women (Newman et al., 2001), increased household de-
mands, particularly linked to child care, can induce more
daily stressful challenges and are linked to lower morning
glucocorticoid levels (Adam & Gunnar, 2001). Interest-
ingly, parity is also associated with elevations in the dias-
tolic blood pressure observed during the daytime (James,
Cates, Pickering, & Laragh, 1989), suggesting that multiple
physiological systems, in multiple states (i.e., basal or
stimulated), can be modified by parity. This result suggests
that parity could have a significant impact on allostatic
load in mothers and/or children.
Inf luences of Early Adversities on
Brain Development
Every day, parents observe the growing behavioral reper-
toire of infants and young children, as well as the corre-
sponding changes in cognitive and emotional functions.
These changes are thought to be related to normal brain de-
velopment, particularly to the growth of the hippocampus
and frontal lobe regions from infancy to childhood. Results
of various studies assessing developmental changes in brain
structures showed that the volumes of whole brain and
frontal and temporal lobes increase rapidly during the first
2 years after birth, followed by a more gradual expansion
restricted to white matter (Matsuzawa et al., 2001; Pfeffer-
baum et al., 1994). Examination of the spatial and temporal
patterns of brain growth, brain shrinkage, and cortical
thinning over time may help to explain the cognitive and
behavioral changes that occur from infancy to childhood.
The volume of the hippocampal formation increases
sharply until the age of 2 years (Utsunomiya, Takano,
Okazaki, & Mitsudome, 1999), and the prefrontal volume
increases rapidly between 8 and 14 years of age (Kanemura
et al., 1999). Late growth in prefrontal volumes is consis-
tent with data showing that this region is known to develop
latest in terms of myelination and synaptic density
(Yakovlev, 1967). In summary, by the age of 2 years, the
hippocampal formation has stabilized, and the prefrontal
cortex volume presents a sharp increase in volume by the
age of 8. The observed maturation in the frontal lobes has
been shown to correlate with measures of cognitive func-
tioning during childhood and adolescence (Reiss, Abrams,
Singer, Ross, & Denckla, 1996; Sowell, Thompson, Tess-
ner, & Toga, 2001).
Although the changes in brain structures observed dur-
ing childhood and adolescence are likely maturational in
nature and may be related to pubertal and hormonal
changes that occur during the adolescent years, it is impor-
tant to underline that, as summarized earlier, various ani-
mal studies have shown differential changes in dendritic
arborization and cortical thickening of the hippocampus as
a function of enriched, stressful, or demanding environ-
mental experiences. It is thus conceivable that exposure to
early adversities (prenatally and/or postnatally) in devel-
oping children might impact the development of the brain
structures involved in the response to stress ( hippocampus,
amygdala, and frontal lobes; see earlier discussion) and
lead them to become more reactive to stress in adulthood.
A recent study by Gilbertson and collaborators (2002)
goes along with this suggestion. Earlier studies assessing
the volume of the hippocampus in adult individuals who
were exposed to traumatic events and who developed Post-
traumatic Stress Disorder (PTSD) revealed that these
individuals present smaller hippocampal volumes when
compared to individuals exposed to the same trauma, but
who did not develop PTSD (Bremner, 2002, 2003;
Vythilingam et al., 2002). These results led to the sugges-
tion that exposure to a traumatic event induces an atrophy
of the adult hippocampus due to the neurotoxic effects of
glucocorticoids on the hippocampus (the “neurotoxicity
hypothesis” or “glucocorticoid-cascade hypothesis”;
Jacobson & Sapolsky, 1991; Sapolsky, Krey, & McEwen,
1986). However, in 2002, Gilbertson et al. tested another
possible hypothesis (called the “ vulnerability hypothesis”),
whereby predetermined smaller hippocampal volumes
could explain increased reactivity to traumatic events in
adults exposed to trauma, leading them to develop PTSD
when exposed to a traumatic experience. To test this hy-
pothesis, these authors measured hippocampal volumes in
Vietnam War veterans who developed PTSD (PTSD+
group) and in others who did not develop PTSD (the
PTSD− group) in response to the trauma of war. By com-
paring the hippocampal volumes of these two groups, they
replicated earlier findings showing that the PTSD+ group
had smaller hippocampal volumes then the PTSD− group
(the neurotoxicity hypothesis). However, in the same study,
they also measured the hippocampal volumes of the ho-
mozygotic twin brother of each of the Vietnam War veter-
ans (PTSD+ and PTSD−), who never went to war. Here,
they showed that the homozygotic twin brothers of the
PTSD+ group also had small hippocampal volumes when
compared to the homozygotic twin brothers of the PTSD−
group. These results strongly suggest that the men who
went to war and developed PTSD entered the war zone with
a smaller hippocampal volume to begin with, relative to the
men who went to war and did not develop PTSD (the vul-
nerability hypothesis). Consequently, hippocampal volume
may actually be a preexisting condition that increases vul-

nerability to PTSD upon exposure to a traumatic experi-
ence, rather than (or along with) being a consequence of
the trauma.
Still, the smaller hippocampal volumes in the men who
developed PTSD on exposure to war could have been deter-
mined by early exposure to stress, which could then have
delayed the development of this structure and rendered
these individuals more vulnerable to the effects of stress
and trauma later in life. Indeed, it is important to remind
the reader that stress, environmental enrichment, and envi-
ronmental demands are among the most potent inducers of
changes in neurogenesis and/or dendritic arborization in
the hippocampus, documented to lead to changes in hip-
pocampal volumes.
Based on these data, we believe that there is an urgent
need to test the influence of early adversity on the develop-
ing hippocampus (and other brain structures). Here, two
contradictory hypotheses emerge with regard to the influ-
ence that early adversity might have on the development of
the hippocampus. First, it could be postulated that children
facing adversity due to lower levels of environmental en-
richment and/or higher levels of stress could eventually
present a delay in the development of the hippocampus
(either due to a decrease in neurogenesis or a stress-in-
duced decrease in dendritic arborization), which could
eventually result in smaller hippocampal volumes in chil-
dren facing early adversity when compared to children who
do not. If this is the case, one could predict that smaller
hippocampal volumes in children facing adversities could
render these children more vulnerable to the effects of
stress on both cognition and mental health. However, an-
other hypothesis can also be proposed with regard to the
development of the hippocampus in the face of adversity.
Indeed, a wealth of animal data has now shown that hip-
pocampal volume increases in relation to environmental de-
mands due to the presence of stressful situations (see
earlier discussion). It may thus be possible that growing up
in adversity could lead to significant changes in hippocam-
pal neurogenesis and/or growth and contribute to larger
hippocampal volumes. If this is the case, one would have to
predict that the larger hippocampal volumes in children
facing adversity could render these children less vulnerable
to the effects of stress on both cognition and mental health.
However, both hypotheses could coexist. Developmen-
tal pathways leading to small versus large hippocampi in
children facing adversities could be determined by the
child’s perception of what the adverse environment can
offer. If nothing is perceived as coming out of the adverse
environment, stress could impact negatively on the devel-
oping hippocampus and lead to smaller volumes and to an
General Conclusion 615
increased vulnerability to stress in future years. However,
if exposure to adverse events pushes the child to search
for more appropriate environments (increased demands),
this could impact positively on the developing hippocam-
pus, lead to larger volumes and, consequently, to a de-
creased vulnerability to stress in future years. If this is
the case, then for the first time, a structural and biological
basis of resilience would be described. However, the pro-
cess that leads a child to believe that a neglectful environ-
ment has nothing to offer ( learned helplessness) or that
pushes him or her to search for a better environment
(meeting demands) is one of the most intriguing processes
that the field of developmental psychopathology might
have to face in the next decade.
GENERAL CONCLUSION
The concepts of allostasis and allostatic load are inclusive
of what we mean by stress, but they are much broader be-
cause they include aspects of lifestyle as well as genetic in-
fluences and developmental effects, including early life
experiences and adversities. In this way, allostasis and al-
lostatic load provide a general conceptual framework that
allows us to evaluate the overall impact of the physical and
social environment on individuals and groups of individu-
als. It should be emphasized that, although most of the
work done so far has focused on the role of HPA activity
and autonomic nervous system reactivity in these nature-
nurture interactions, the allostasis/allostatic load model
can be generalized to other physiological systems that re-
spond to environmental stimuli. In other words, allostasis
and allostatic load attempt to embody a general biological
principle: that the systems that help protect the body and
promote adaptation in the short term can also participate in
pathophysiological processes when they are overused or in-
efficiently managed.
The most important feature of allostatic load is that it
operates gradually over long periods of time in the life
of an individual. In fact, as summarized in this chapter, in-
fluences of genetic factors and early experiences, when
coupled with the subsequent life experiences of each indi-
vidual, exert a lifelong effect on the physiology of an indi-
vidual and alter the risk for developing a variety of
pathophysiological conditions and diseases later in life as
well as the rate of certain aspects of the aging process.
More important, given that the primary stress mediators of
allostatic load can access the brain, they can alter the way
incoming information is processed, leading to important
616 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
differences in the interpretation of events as being stressful
(threatening) or nonstressful (nonthreatening).
This multidisciplinary view of stress as a form of allo-
static load should eventually allow us to identify very early
in the life of an individual what are the potential risk fac-
tors for the negative effects of stress on physical and men-
tal health. For example, personality traits such as anger,
negative affect, low self-esteem, and emotional inhibition
modify HPA and autonomic nervous system reactivity on
an acute and/or chronic basis (for an example, see
Kirschbaum, Prussner, et al., 1995). These changes, in turn,
contribute to allostatic load when they represent a lifelong
pattern of response to challenges. We have seen that these
personality traits might themselves be the result of early
life experiences as well as reflections of genetic factors.
Fortunately, none of these traits, or the genetic and/or envi-
ronmental factors that produce them, reflects an irre-
versible change in either behavior or allostatic load, and
there are many intervention strategies that are likely to be
very helpful early in development as well as later in life.
However, before intervening in the early and/or later life
period, one has to detect the presence of a chronic stress
state. This is what allostatic load is about: detecting, in
order to prevent.
REFERENCES
Adam, E. K., & Gunnar, M. R. (2001). Relationship functioning and
home and work demands predict individual differences in diurnal cor-
tisol patterns in women. Psychoneuroendocrinology, 26(2), 189–208.
Adelstein, A. M. (1980). Life-style in occupational cancer. Journal of
Toxicology and Environmental Health, 6(5/6), 953–962.
Ader, R. (1969). Early experiences accelerate maturation of the 24-hour
adrenocortical rhythm. Science, 163(872), 1225–1226.
Adler, N. E., Boyce, W. T., Chesney, M. A., Cohen, S., Folkman, S.,
Kahn, R. L., et al. (1994). Socioeconomic status and health: The chal-
lenge of the gradient. American Psychologist, 49(1), 15–24.
Altemus, M., Deuster, P. A., Galliven, E., Carter, C. S., & Gold, P. W.
(1995). Suppression of hypothalmic-pituitary-adrenal axis responses
to stress in lactating women. Journal of Clinical Endocrinology and
Metabolism, 80(10), 2954–2959.
Altman, J., & Das, G. D. (1965). Autoradiographic and histological evi-
dence of postnatal hippocampal neurogenesis in rats. Journal of Com-
parative Neurology, 124(3), 319–335.
al-Wabel, A., al-Janadi, M., & Raziuddin, S. (1993). Cytokine profile of
viral and autoimmune chronic active hepatitis. Journal of Allergy and
Clinical Immunology, 92(6), 902–908.
An, P., Rice, T., Perusse, L., Borecki, I. B., Gagnon, J., Leon, A. S., et al.
(2000). Complex segregation analysis of blood pressure and heart
rate measured before and after a 20-week endurance exercise training
program: The HERITAGE Family Study. American Journal of Hyper-
tension, 13(5, Pt. 1), 488–497.
Andersen, S. L. (2003). Trajectories of brain development: Point of vul-
nerability or window of opportunity? Neuroscience and Biobehavioral
Reviews, 27(1/2), 3–18.
Anderson, A. K., Phelps, E. A. (2001). Lesions of the human amygdala
impair enhanced perception of emotionally salient events. Nature,
411, 305–309.
Anisman, H., Zaharia, M. D., Meaney, M. J., & Merali, Z. (1998). Do
early-life events permanently alter behavioral and hormonal re-
sponses to stressors? International Journal of Developmental Neuro-
science, 16(3/4), 149–164.
Araneo, B., & Daynes, R. (1995). Dehydroepiandrosterone functions as
more than an antiglucocorticoid in preserving immunocompetence
after thermal injury. Endocrinology, 136(2), 393–401.
Ashman, S. B., Dawson, G., Panagiotides, H., Yamada, E., & Wilkinson,
C. W. (2002). Stress hormone levels of children of depressed mothers.
Development and Psychopathology, 14(2), 333–349.
Azar, R., Zoccolillo, M., Paquette, D., Quiros, E., Baltzer, F., & Trem-
blay, R. E. (2004). Cortisol levels and conduct disorder in adolescent
mothers. Journal of the American Academy of Child and Adolescent
Psychiatry, 43(4), 461–472.
Baddeley, A. D. (1999). Essentials of human memory. London: Tay-
lor & Francis.
Balomenos, D., Rumold, R., & Theofilopoulos, A. N. (1998). Interferon-
gamma is required for lupus-like disease and lymphoaccumulation in
MRL-lpr mice. Journal of Clinical Investigation, 101(2), 364–371.
Barker, D. J., Hales, C. N., Fall, C. H., Osmond, C., Phipps, K., & Clark,
P. M. (1993). Type 2 (non-insulin-dependent) diabetes mellitus, hy-
pertension and hyperlipidaemia (syndrome X): Relation to reduced
fetal growth. Diabetologia, 36(1), 62–67.
Bartels, M., de Geus, E. J., Kirschbaum, C., Sluyter, F., & Boomsma,
D. I. (2003). Heritability of daytime cortisol levels in children. Be-
havior Genetics, 33(4), 421–433.
Bartels, M., Van den Berg, M., Sluyter, F., Boomsma, D. I., & de Geus,
E. J. (2003). Heritability of cortisol levels: Review and simultaneous
analysis of twin studies. Psychoneuroendocrinology, 28(2), 121–137.
Beauman, D. E. (2000). Regulation of nutrient partitioning during lacta-
tion: Homeostasis and homeorhesis revisited. In P. J. Cronje (Ed.),
Ruminant physiology: Digestion, metabolism, and growth and repro-
duction (pp. 311–327). New York: CAB Publishing.
Beeghly, M., Bretherton, I., & Mervis, C. (1986). Mother’s internal
state language to toddlers. British Journal of Developmental Psychol-
ogy, 4, 247–260.
Beeghly, M., & Cicchetti, D. (1994). Child maltreatment, attachment and
the self system: Emergence of an internal state lexicon in toddlers at
high social risk. Development and Psychopathology, 6, 5–30.
Berk, L. S., Tan, S. A., Fry, W. F., Napier, B. J., Lee, J. W., Hubbard, R.
W., et al. (1989). Neuroendocrine and stress hormone changes dur-
ing mirthful laughter. American Journal of the Medical Sciences,
298(6), 390–396.
Berman, M. E., Tracy, J. I., & Coccaro, E. F. (1997). The serotonin
hypothesis of aggression revisited. Clinical Psychology Review,
17(6), 651–665.
Bigler, E. D. (2001). Frontal lobe pathology and antisocial personality
disorder. Archives of General Psychiatry, 58, 609–611.
Birmaher, B., Rabin, B. S., Garcia, M. R., Jain, U., Whiteside, T. L.,
Williamson, D. E., et al. (1994). Cellular immunity in depressed, con-
duct disorder, and normal adolescents: Role of adverse life events.
Journal of the American Academy of Child and Adolescent Psychiatry,
33(5), 671–678.
Blackhurst, G., McElroy, K. P., Kenyon, C. J., Fraser, R., Swan, L., An-
derson, N., et al. (2002). Glucocorticoid receptor binding in twin
pairs is affected by shared environment but not by shared genes. Jour-
nal of Steroid Biochemistry and Molecular Biology, 80(4/5), 395–400.
Bolger, K. E., Patterson, C. J., Thompson, W. W., & Kupersmidt, J. B.
(1995). Psychosocial adjustment among children experiencing persis-

tent and intermittent family economic hardship. Child Development,
66(4), 1107–1129.
Bonnin, F. (1992). Cortisol levels in saliva and mood changes in early
puerperium. Journal of Af fective Disorders, 26(4), 231–239.
Boomsma, D. I., & Plomin, R. (1986). Heart rate and behavior of twins.
Merrill-Palmer Quarterly, 32(2), 141–151.
Boukydis, C. F., & Burgess, R. L. (1982). Adult physiological response to
infant cries: Effects of temperament of infant, parental status, and
gender. Child Development, 53(5), 1291–1298.
Bradley, R. H., & Corwyn, R. F. (2002). Socioeconomic status and child
development. Annual Review of Psychology, 53, 371–399.
Breier, A., Albus, M., Pickar, D., Zahn, T. P., Wolkowitz, O. M., & Paul,
S. M. (1987). Controllable and uncontrollable stress in humans: Al-
terations in mood and neuroendocrine and psychophysiological func-
tion. American Journal of Psychiatry, 144(11), 1419–1425.
Bremner, J. D. (2002). Neuroimaging studies in post-traumatic stress dis-
order. Current Psychiatry Reports, 4(4), 254–263.
Bremner, J. D. (2003). Functional neuroanatomical correlates of trau-
matic stress revisited 7 years later, this time with data. Psychophar-
macology Bulletin, 37(2), 6–25.
Brennan, P. A., & Raine, A. (1997). Biosocial bases of antisocial behav-
ior: Psychophysiological, neurological, and cognitive factors. Clinical
Psychology Review, 17(6), 589–604.
Breslau, N., Chilcoat, H., DelDotto, J., Andreski, P., & Brown, G.
(1996). Low birth weight and neurocognitive status at six years of
age. Biological Psychiatry, 40(5), 389–397.
Bridges, R. S. (1984). A quantitative analysis of the roles of dosage,
sequence, and duration of estradiol and progesterone exposure in
the regulation of maternal behavior in the rat. Endocrinology,
114(3), 930–940.
Bridges, R. S., Numan, M., Ronsheim, P. M., Mann, P. E., & Lupini,
C. E. (1990). Central prolactin infusions stimulate maternal be-
havior in steroid-treated, nulliparous female rats. Proceedings of
the National Academy of Sciences of the United States of America,
87(20), 8003–8007.
Brindley, D. N., & Rolland, Y. (1989). Possible connections between stress,
diabetes, obesity, hypertension and altered lipoprotein metabolism
that may result in atherosclerosis. Clinical Science, 77(5), 453–461.
Broadhead, W. E., Kaplan, B. H., James, S. A., Wagner, E. H., Schoen-
bach, V. J., Grimson, R., et al. (1983). The epidemiologic evidence for
a relationship between social support and health. American Journal of
Epidemiology, 117(5), 521–537.
Bronfenbrenner, U., & Ceci, S. J. (1994). Nature-nurture reconceptual-
ized in developmental perspective: A bioecological model. Psycho-
logical Review, 101(4), 568–586.
Brooks-Gunn, J., & Duncan, G. J. (1997). The effects of poverty on chil-
dren. Future of Children, 7(2), 55–71.
Buitelaar, J. K., Huizink, A. C., Mulder, E. J., de Medina, P. G., & Visser,
G. H. (2003). Prenatal stress and cognitive development and tempera-
ment in infants. Neurobiology of Aging, 24(Suppl. 1), S53–S60.
Bunge, S. A., Ochsner, K. N., Desmond, J. E., Glover, G. H., & Gabrieli,
J. D. (2001). Prefrontal regions involved in keeping information in
and out of mind. Brain, 124, 2074–2086.
Buydens-Branchey, L., & Branchey, M. (2004). Cocaine addicts with
conduct disorder are typified by decreased cortisol responsivity and
high plasma levels of DHEA-S. Neuropsychobiology, 50(2), 161–166.
Buydens-Branchey, L., Branchey, M., Hudson, J., & Fergeson, P. (2000).
Low HDL cholesterol, aggression and altered central serotonergic ac-
tivity. Psychiatry Research, 93(2), 93–102.
Cahill, L., Prins, B., Weber, M., & McGaugh, J. L. (1994). Beta-adrener-
gic activation and memory for emotional events. Nature, 371(6499),
702–704.
References 617
Cameron, H. A., & Gould, E. (1994). Adult neurogenesis is regulated by
adrenal steroids in the dentate gyrus. Neuroscience, 61(2), 203–209.
Cameron, H. A., & McKay, R. D. (1999). Restoring production of hip-
pocampal neurons in old age. Nature Neuroscience, 2(10), 894–897.
Cameron, H. A., Woolley, C. S., McEwen, B. S., & Gould, E. (1993). Dif-
ferentiation of newly born neurons and glia in the dentate gyrus of
the adult rat. Neuroscience, 56(2), 337–344.
Cameron, O. G., Starkman, M. N., & Schteingart, D. E. (1995). The ef-
fect of elevated systemic cortisol levels on plasma catecholamines in
Cushing’s syndrome patients with and without depressed mood. Jour-
nal of Psychiatric Research, 29(5), 347–360.
Cannon, W. (1929). The wisdom of the body. Physiological Review,
9, 399– 431.
Carter, D. A., & Lightman, S. L. (1987). Oxytocin responses to stress
in lactating and hyperprolactinaemic rats. Neuroendocrinology,
46(6), 532–537.
Case, R. (1985). Intellectual development: Birth to adulthood. New York:
Academic Press.
Caspi, A., & Moffitt, T. E. (1995). The continuity of maladaptive behav-
ior: From description to understanding in the study of antisocial be-
havior. In D. Cicchetti & D. J. Cohen (Eds.), Developmental
psychopathology: Vol. 2. Risk, disorder and adaptation (pp. 472–511).
New York: Wiley.
Cefalu, W. T., Wang, Z. Q., Werbel, S., Bell-Farrow, A., Crouse, J. R.,
III, Hinson, W. H., et al. (1995). Contribution of visceral fat mass to
the insulin resistance of aging. Metabolism, 44(7), 954–959.
Champagne, F. A., Francis, D. D., Mar, A., & Meaney, M. J. (2003).
Variations in maternal care in the rat as a mediating inf luence for the
effects of environment on development. Physiology and Behavior,
79(3), 359–371.
Chen, C. C., Lu, F. H., Wu, J. S., & Chang, C. J. (2001). Correlation be-
tween serum lipid concentrations and psychological distress. Psychi-
atry Research, 102(2), 153–162.
Chen, D. C., Nommsen-Rivers, L., Dewey, K. G., & Lonnerdal, B. (1998).
Stress during labor and delivery and early lactation performance.
American Journal of Clinical Nutrition, 68(2), 335–344.
Chomsky, N. (1972). Language and mind. San Diego: Harcourt Brace
Jovanovich.
Chrousos, G. P. (1995). The hypothalamic-pituitary-adrenal axis and im-
mune-mediated inf lammation. New England Journal of Medicine,
332(20), 1351–1362.
Chrousos, G. P., & Elenkov, I. (2000). Interactions of the endocrine and
immune systems. In L. DeGroot (Ed.), Endocrinology (4th ed.,
pp. 571–586). Philadelphia: Saunders.
Cicchetti, D. (1991). Fractures in the crystal: Developmental psychopathol-
ogy and the emergence of self. Developmental Review, 11(3), 271–287.
Cicchetti, D. (2002). The impact of social experience on neurobiological
systems: Illustration from a constructivist view of child maltreat-
ment. Cognitive Development, 17(3), 1407–1428.
Cicchetti, D., & Rogosch, F. A. (2001). Diverse patterns of neuroen-
docrine activity in maltreated children. Development and Psycho-
pathology, 13(3), 677–693.
Cicchetti, D., Rogosch, F. A., Maughan, A., Toth, S. L., & Bruce, J.
(2003). False belief understanding in maltreated children. Develop-
ment and Psychopathology, 15(4), 1067–1091.
Clauw, D. J., & Chrousos, G. P. (1997). Chronic pain and fatigue syn-
dromes: Overlapping clinical and neuroendocrine features and poten-
tial pathogenic mechanisms. Neuroimmunomodulation, 4(3), 134–153.
Clayton, N. S., & Krebs, J. R. (1994). Hippocampal growth and attrition
in birds affected by experience. Proceedings of the National Academy
of Sciences of the United States of America, 91(16), 7410–7414.
618 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
Coccaro, E. F. (1992). Impulsive aggression and central serotonergic sys-
tem function in humans: An example of a dimensional brain behavior
relationship. International Clinical Psychopharmacology, 7(1), 3–12.
Coelho, R., Silva, C., Maia, A., Prata, J., & Barros, H. (1999). Bone min-
eral density and depression: A community study in women. Journal of
Psychosomatic Research, 46(1), 29–35.
Cohen, R. M., Weingartner, H., Smallberg, S. A., Pickar, D., & Murphy,
D. L. (1982). Effort and cognition in depression. Archives of General
Psychiatry, 39(5), 593–597.
Cohen, S. (1988). Psychosocial models of the role of social support in the
etiology of physical disease. Health Psychology, 7(3), 269–297.
Cohen, S., Line, S., Manuck, S. B., Rabin, B. S., Heise, E. R., & Kaplan,
J. R. (1997). Chronic social stress, social status, and susceptibility to
upper respiratory infections in nonhuman primates. Psychosomatic
Medicine, 59(3), 213–221.
Cohen, S., Tyrrell, D. A., & Smith, A. P. (1991). Psychological stress and
susceptibility to the common cold. New England Journal of Medicine,
325(9), 606–612.
Conger, R. D., Patterson, G. R., & Ge, X. (1995). It takes two to repli-
cate: A mediational model for the impact of parents’ stress on adoles-
cent adjustment. Child Development, 66(1), 80–97.
Connolly, J. D., Goodale, M. A., Menon, R. S., & Munoz, D. P. (2002).
Human fMRI evidence for the neural correlates of preparatory set.
Nature Neuroscience, 5, 1345–1352.
Cooley-Quille, M., & Lorion, R. (1999). Adolescents’ exposure to com-
munity violence: Sleep and psychophysiological functioning. Journal
of Community Psychology, 27(4), 367–375.
Corcoran, M. E., & Chaudry, A. (1997). The dynamics of childhood
poverty. Future Child, 7(2), 40–54.
Coster, W. J., Gersten, M. S., Beeghly, M., & Cicchetti, D. (1989). Com-
municative functioning in maltreated toddlers. Developmental Psy-
chology, 25(6), 1020–1029.
Crimmins, E. M., Johnston, M., Hayward, M., & Seeman, T. (2003). Age
differences in allostatic load: An index of physiological dysregula-
tion. Experimental Gerontology, 38(7), 731–734.
Crofford, L. J., Jacobson, J., & Young, E. (1999). Modeling the involve-
ment of the hypothalamic-pituitary-adrenal and hypothalamic-pitu-
itary-gonadal axes in autoimmune and stress-related rheumatic
syndromes in women. Journal of Women’s Health, 8(2), 203–215.
Curtis, W. J., & Cicchetti, D. (2003). Moving research on resilience into
the 21st century: Theoretical and methodological considerations in
examining the biological contributors to resilience. Development and
Psychopathology, 15(3), 773–810.
Cutting, A. L., & Dunn, J. (1999). Theory of mind, emotion understand-
ing, language, and family background: Individual differences and in-
terrelations. Child Development, 70(4), 853–865.
Da Costa, D., Larouche, J., Dritsa, M., & Brender, W. (2000). Psychoso-
cial correlates of prepartum and postpartum depressed mood. Journal
of Af fective Disorders, 59(1), 31–40.
Davachi, L., & Wagner, A. D. (2002). Hippocampal contributions to
episodic encoding: Insights from relational and item-based learning.
Journal of Neurophysiology, 88, 982—990.
Davis, E. P., Donzella, B., Krueger, W. K., & Gunnar, M. R. (1999). The
start of a new school year: Individual differences in salivary cortisol
response in relation to child temperament. Developmental Psychobiol-
ogy, 35(3), 188–196.
Davis, M. C., Matthews, K. A., & McGrath, C. E. (2000). Hostile atti-
tudes predict elevated vascular resistance during interpersonal stress
in men and women. Psychosomatic Medicine, 62(1), 17–25.
Deater-Deckard, K., Dodge, K. A., Bates, J. E., & Pettit, G. S. (1996).
Physical discipline among African American and European American
mothers: Links to children’s externalizing behaviors. Developmental
Psychology, 32(6), 1065–1072.
de Geus, E. J. (2002). Introducing genetic psychophysiology. Biological
Psychology, 61(1/2), 1–10.
de Haan, M., Gunnar, M. R., Tout, K., Hart, J., & Stansbury, K. (1998).
Familiar and novel contexts yield different associations between cor-
tisol and behavior among 2-year-old children. Developmental Psy-
chobiology, 33(1), 93–101.
De Kloet, E. R., Vreugdenhil, E., Oitzl, M. S., & Joels, M. (1998). Brain
corticosteroid receptor balance in health and disease. Endocrine Re-
views, 19(3), 269–301.
Dent, G. W., Smith, M. A., & Levine, S. (2000). Rapid induction of cor-
ticotropin-releasing hormone gene transcription in the paraventricu-
lar nucleus of the developing rat. Endocrinology, 141(5), 1593–1598.
Dettling, A. C., Gunnar, M. R., & Donzella, B. (1999). Cortisol levels of
young children in full-day childcare centers: Relations with age and
temperament. Psychoneuroendocrinology, 24(5), 519–536.
Dhabhar, F. S., & McEwen, B. S. (1999). Enhancing versus suppressive
effects of stress hormones on skin immune function. Proceedings of
the National Academy of Sciences of the United States of America,
96(3), 1059–1064.
Dickerson, S. S., & Kemeny, M. E. (2002). Acute stressors and corti-
sol reactivity: A meta-analytic review. Psychosomatic Medicine,
54, 105–123.
Ditto, B. (1993). Familial inf luences on heart rate, blood pressure, and
self-report anxiety responses to stress: Results from 100 twin pairs.
Psychophysiology, 30(6), 635–645.
Dmitrieva, T. N., Oades, R. D., Hauffa, B. P., & Eggers, C. (2001). Dehy-
droepiandrosterone sulphate and corticotropin levels are high in young
male patients with conduct disorder: Comparisons for growth factors,
thyroid and gonadal hormones. Neuropsychobiology, 43(3), 134–140.
Dohrenwend, B. P. (2000). The role of adversity and stress in psycho-
pathology: Some evidence and its implications for theory and re-
search. Journal of Health and Social Behavior, 41(1), 1–19.
Dohrenwend, B. S. (1973). Social status and stressful life events. Journal
of Personality and Social Psychology, 28(2), 225–235.
Dohrenwend, B. S., & Dohrenwend, B. P. (1970). Class and race as sta-
tus-related sources of stress. In S. Levine & N. A. Scotch (Eds.), So-
cial stress (pp. 111–140). Chicago: Aldine.
Dubreuil, E., Ditto, B., Dionne, G., Pihl, R. O., Tremblay, R. E., Boivin,
M., et al. (2003). Familiality of heart rate and cardiac-related auto-
nomic activity in five-month-old twins: The Quebec newborn twins
study. Psychophysiology, 40(6), 849–862.
Dunn, J., Bretherton, I., & Munn, P. (1987). Conversations about feeling
states between mothers and their young children. Developmental Psy-
chology, 23, 132–139.
Dunn, J., Brown, J., & Beardsall, L. (1991). Family talk about feeling
states and children’s later understanding of other’s emotions. Devel-
opmental Psychology, 27, 448–455.
Eigsti, I. M., & Cicchetti, D. (2004). The impact of child maltreatment on
expressive syntax at 60 months. Developmental Science, 7(1), 88–102.
Elenkov, I. J., Chrousos, G. P., & Wilder, R. L. (2000). Neuroendocrine
regulation of IL-12 and TNF-alpha / IL-10 balance: Clinical implica-
tions. Annals of the New York Academy of Sciences, 917, 94–105.
Elenkov, I. J., Papanicolaou, D. A., Wilder, R. L., & Chrousos, G. P.
(1996). Modulatory effects of glucocorticoids and catecholamines on
human interleukin-12 and interleukin-10 production: Clinical impli-
cations. Proceedings of the Association of American Physicians,
108(5), 374–381.
Eriksson, P. S., Perfilieva, E., Bjork-Eriksson, T., Alborn, A. M., Nord-
borg, C., Peterson, D. A., et al. (1998). Neurogenesis in the adult
human hippocampus. Nature Medicine, 4(11), 1313–1317.

Essex, M. J., Klein, M. H., Cho, E., & Kalin, N. H. (2002). Maternal
stress beginning in infancy may sensitize children to later stress ex-
posure: Effects on cortisol and behavior. Biological Psychiatry,
52(8), 776–784.
Evans, D. M., Gillespie, N. A., & Martin, N. G. (2002). Biometrical ge-
netics. Biological Psychology, 61(1), 33–51.
Evans, G. W. (2003). A multimethodological analysis of cumulative risk
and allostatic load among rural children. Developmental Psychology,
39(5), 924–933.
Evans, G. W., & English, K. (2002). The environment of poverty: Multi-
ple stressor exposure, psychophysiological stress, and socioemotional
adjustment. Child Development, 73(4), 1238–1248.
Evans, G. W., & Marcynyszyn, L. A. (2004). Environmental justice, cu-
mulative environmental risk, and health among low- and middle-in-
come children in upstate New York. American Journal of Public
Health, 94(11), 1942–1944.
Fan, J., Snodgrass, J., & Bilder, R. M. (2003). Functional magnetic resonance
imaging of source versus item memory. Neuroreport, 2, 2275–2281.
Felitti, V. J., Anda, R. F., Nordenberg, D., Williamson, D. F., Spitz, A.
M., Edwards, V., et al. (1998). Relationship of childhood abuse and
household dysfunction to many of the leading causes of death in
adults: The Adverse Childhood Experiences (ACE) Study. American
Journal of Preventive Medicine, 14(4), 245–258.
Field, T. (1994). The effects of mother’s physical and emotional un-
availability on emotion regulation. In N. A. Fox (Ed.), The develop-
ment of emotion regulation (pp. 208–227). Chicago: University of
Chicago Press.
Fleming, A. S., Ruble, D., Krieger, H., & Wong, P. Y. (1997). Hormonal
and experiential correlates of maternal responsiveness during preg-
nancy and the puerperium in human mothers. Hormones and Behav-
ior, 31(2), 145–158.
Fleming, A. S., Steiner, M., & Corter, C. (1997). Cortisol, hedonics, and
maternal responsiveness in human mothers. Hormones and Behavior,
32(2), 85–98.
Flinn, M. V., & England, B. G. (1997). Social economics of childhood
glucocorticoid stress response and health. American Journal of Phys-
ical Anthropology, 102(1), 33–53.
Folkman, S., Schaefer, C., & Lazarus, R. S. (1979). Cognitive processes
as mediators of stress and coping. In V. Hamilton & D. W. Warburton
(Eds.), Human stress and cognition: An information processing ap-
proach (pp. 265–298). New York: Wiley.
Fournie, G. J., Cautain, B., Xystrakis, E., Damoiseaux, J., Mas, M., La-
grange, D., et al. (2001). Cellular and genetic factors involved in the
difference between Brown Norway and Lewis rats to develop respec-
tively type-2 and type-1 immune-mediated diseases. Immunological
Reviews, 184, 145–160.
Francis, D. D., Champagne, F. A., Liu, D., & Meaney, M. J. (1999). Ma-
ternal care, gene expression, and the development of individual dif-
ferences in stress reactivity. Annals of the New York Academy of
Sciences, 896, 66–84.
Francis, D. D., Diorio, J., Liu, D., & Meaney, M. J. (1999). Nongenomic
transmission across generations of maternal behavior and stress re-
sponses in the rat. Science, 286(5442), 1155–1158.
Frick, P. J. (1998). Conduct disorders and severe antisocial behavior. New
York: Plenum Press.
Froehlich, J. C., Zink, R. W., Li, T. K., & Christian, J. C. (2000). Analy-
sis of heritability of hormonal responses to alcohol in twins: Beta-en-
dorphin as a potential biomarker of genetic risk for alcoholism.
Alcoholism, Clinical and Experimental Research, 24(3), 265–277.
Fuchs, E., Uno, H., & Flugge, G. (1995). Chronic psychosocial stress in-
duces morphological alterations in hippocampal pyramidal neurons
of the tree shrew. Brain Research, 673(2), 275–282.
References 619
Galovski, T. E., Blanchard, E. B., Malta, L. S., & Freidenberg, B. M.
(2003). The psychophsiology of aggressive drivers: Comparison to
non-aggressive drivers and pre- to post-treatment change following a
cognitive-behavioural treatment. Behaviour Research and Therapy,
41(9), 1055–1067.
Garcia-Leon, A., Reyes del Paso, G. A., Robles, H., & Vila, J. (2003).
Relative effects of harassment, frustration, and task characteristics
on cardiovascular reactivity. International Journal of Psychophysiol-
ogy, 47(2), 159–173.
Gerin, W., Litt, M. D., Deich, J., & Pickering, T. G. (1996). Self-efficacy
as a component of active coping: Effects on cardiovascular reactivity.
Journal of Psychosomatic Research, 40(5), 485–493.
Gerlai, R., & Clayton, N. S. (1999). Analysing hippocampal function in
transgenic mice: An ethological perspective. Trends in Neuroscience,
22(2), 47–51.
Gilbertson, M. W., Shenton, M. E., Ciszewski, A., Kasai, K., Lasko, N.
B., Orr, S. P., et al. (2002). Smaller hippocampal volume predicts
pathologic vulnerability to psychological trauma. Nature Neuro-
science, 5(11), 1242–1247.
Golomb, B. A. (1998). Cholesterol and violence: Is there a connection?
Annals of Internal Medicine, 128(6), 478–487.
Golomb, B. A., Stattin, H., & Mednick, S. (2000). Low cholesterol and
violent crime. Journal of Psychiatric Research, 34(4/5), 301–309.
Goodyer, I. M., Herbert, J., Altham, P. M., Pearson, J., Secher, S. M., &
Shiers, H. M. (1996). Adrenal secretion during major depression in 8-
to 16-year-olds: I. Altered diurnal rhythms in salivary cortisol and
dehydroepiandrosterone (DHEA) at presentation. Psychological Med-
icine, 26(2), 245–256.
Goodyer, I. M., Park, R. J., Netherton, C. M., & Herbert, J. (2001). Possi-
ble role of cortisol and dehydroepiandrosterone in human development
and psychopathology. British Journal of Psychiatry, 179, 243–249.
Gopnik, A., & Astington, J. W. (1988). Children’s understanding of rep-
resentational change and its relation to the understanding of false be-
lief and the appearance-reality distinction. Child Development,
59(1), 26–37.
Gould, E., McEwen, B. S., Tanapat, P., Galea, L. A., & Fuchs, E. (1997).
Neurogenesis in the dentate gyrus of the adult tree shrew is regulated
by psychosocial stress and NMDA receptor activation. Journal of
Neuroscience, 17(7), 2492–2498.
Gould, E., Reeves, A. J., Fallah, M., Tanapat, P., Gross, C. G., & Fuchs,
E. (1999). Hippocampal neurogenesis in adult Old World primates.
Proceedings of the National Academy of Sciences of the United States
of America, 96(9), 5263–5267.
Gould, E., Tanapat, P., McEwen, B. S., Flugge, G., & Fuchs, E. (1998).
Proliferation of granule cell precursors in the dentate gyrus of adult
monkeys is diminished by stress. Proceedings of the National Acad-
emy of Sciences of the United States of America, 95(6), 3168–3171.
Grace, J. T. (1993). Mothers’ self-reports of parenthood across the first 6
months postpartum. Research in Nursing and Health, 16(6), 431–439.
Grajeda, R., & Perez-Escamilla, R. (2002). Stress during labor and de-
livery is associated with delayed onset of lactation among urban
Guatemalan women. Journal of Nutrition, 132(10), 3055–3060.
Gray, J. A. (1982). The neurophysiology of anxiety: An enquiry into the
functions of the septo-hippocampal system. Oxford: Oxford Univer-
sity Press.
Gray, J. A. (1987). The psychology of fear and stress (2nd ed.). Cam-
bridge, MA: Cambridge University Press.
Griep, E. N., Boersma, J. W., Lentjes, E. G., Prins, A. P., van der Korst,
J. K., & de Kloet, E. R. (1998). Function of the hypothalamic-pitu-
itary-adrenal axis in patients with fibromyalgia and low back pain.
Journal of Rheumatology, 25(7), 1374–1381.
620 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
Gunnar, M. R., & Donzella, B. (2002). Social regulation of the cortisol
levels in early human development. Psychoneuroendocrinology,
27(1/2), 199–220.
Gunnar, M. R., Morison, S. J., Chisholm, K., & Schuder, M. (2001). Sali-
vary cortisol levels in children adopted from Romanian orphanages.
Development and Psychopathology, 13(3), 611–628.
Gunnar, M. R., Tout, K., de Haan, M., Pierce, S., & Stansbury, K.
(1997). Temperament, social competence, and adrenocortical activity
in preschoolers. Developmental Psychobiology, 31(1), 65–85.
Gunnar, M. R., & Vazquez, D. M. (2001). Low cortisol and a f lattening of
expected daytime rhythm: Potential indices of risk in human develop-
ment. Development and Psychopathology, 13(3), 515–538.
Gutierrez, M. A., Garcia, M. E., Rodriguez, J. A., Rivero, S., & Jacobelli,
S. (1998). Hypothalamic-pituitary-adrenal axis function and prolactin
secretion in systemic lupus erythematosus. Lupus, 7(6), 404–408.
Haan, M. N., Kaplan, G. A., & Syme, S. L. (1989). Socioeconomic sta-
tus and health: Old observations and new thoughts. In J. Bunker, D.
Gomby, & B. Kehrer (Eds.), Pathways to health: The role of social
factors (pp. 31–43). Menlo Park, CA: Henry H. Kaiser Family
Foundation.
Haapasalo, J., & Tremblay, R. E. (1994). Physically aggressive boys
from ages 6 to 12: Family background, parenting behavior, and pre-
diction of delinquency. Journal of Consulting and Clinical Psychol-
ogy, 62(5), 1044–1052.
Hall, R. C., Popkin, M. K., Stickney, S. K., & Gardner, E. R. (1979). Pre-
sentation of the steroid psychoses. Journal of Nervous and Mental
Diseases, 167(4), 229–236.
Han, D. H., Hansen, P. A., Chen, M. M., & Holloszy, J. O. (1998). DHEA
treatment reduces fat accumulation and protects against insulin re-
sistance in male rats. Journals of Gerontology. Series A, Biological
Sciences and Medical Sciences, 53(1), B19–B24.
Hansen, P. A., Han, D. H., Nolte, L. A., Chen, M., & Holloszy, J. O.
(1997). DHEA protects against visceral obesity and muscle insulin
resistance in rats fed a high-fat diet. American Journal of Physiology,
273(5, Pt. 2), R1704–R1708.
Hanson, T. L., McLanahan, S., & Thomson, E. (1997). Economic re-
sources, parental practices, and children’s well-being. In G. J. Dun-
can & J. Brooks-Gunn (Eds.), Consequences of growing up poor
(pp. 190–238). New York: Russell Sage Foundation.
Harbuz, M. S., Jessop, D. S., & Lightman, S. L. (1997). Hypothalamo-
pituitary-adrenal activity in experimental models of autoimmune-
inf lammatory disease. In J. C. Buckingham, G. E. Gillies, & A. M.
Cowell (Eds.), Stress, stress hormones and the immune system
(pp. 95–123). New York: Wiley.
Hard, E., & Hansen, S. (1985). Reduced fearfulness in the lactating rat.
Physiology and Behavior, 35(4), 641–643.
Hare, R. D. (1965). Psychopathy, fear arousal and anticipated pain. Psy-
chological Reports, 16, 499–502.
Hary, L., Dupouy, J. P., & Chatelain, A. (1981). Pituitary response to bi-
lateral adrenalectomy, metyrapone treatment and ether stress in the
newborn rat. Biology of the Neonate, 39(1/2), 28–36.
Heale, V. R., Vanderwolf, C. H., & Kavaliers, M. (1994). Components of
weasel and fox odors elicit fast wave bursts in the dentate gyrus of
rats. Behavioral Brain Research, 63(2), 159–165.
Healy, B. T. (1992). The heritability of autonomic nervous system
processes. In T. M. Field & P. M. McCabe (Eds.), Stress and coping in
infancy and childhood (pp. 69–82). New York: Erlbaum.
Heckers, S. (2001). Neuroimaging studies of the hippocampus in Schizo-
phrenia. Hippocampus, 11(5), 520–528.
Hedegaard, M., Henriksen, T. B., Sabroe, S., & Secher, N. J. (1993). Psy-
chological distress in pregnancy and preterm delivery. British Med-
ical Journal, 307(6898), 234–239.
Hedegaard, M., Henriksen, T. B., Sabroe, S., & Secher, N. J. (1996). The
relationship between psychological distress during pregnancy and
birth weight for gestational age. Acta Obstetricia et Gynecologica
Scandinavica, 75(1), 32–39.
Heim, C., Newport, D. J., Heit, S., Graham, Y. P., Wilcox, M., Bonsall,
R., et al. (2000). Pituitary-adrenal and autonomic responses to stress
in women after sexual and physical abuse in childhood. Journal of the
American Medical Association, 284(5), 592–597.
Hellhammer, D. H., Buchtal, J., Gutberlet, I., & Kirschbaum, C. (1997).
Social hierarchy and adrenocortical stress reactivity in men. Psy-
choneuroendocrinology, 22(8), 643–650.
Hennessy, K. D., Rabideau, G. J., Cicchetti, D., & Cummings, E. M.
(1994). Responses of physically abused and nonabused children to dif-
ferent forms of interadult anger. Child Development, 65(3), 815–828.
Hertsgaard, L., Gunnar, M., Erickson, M. F., & Nachmias, M. (1995).
Adrenocortical responses to the Strange Situation in infants with dis-
organized/disoriented attachment relationships. Child Development,
66(4), 1100–1106.
Hessl, D., Dawson, G., Frey, K., Panagiotides, H., Self, H., Yamada, E.,
et al. (1998). A longitudinal study of children of depressed mothers:
Psychobiological findings related to stress. In D. M. Hann, L. C.
Huffman, K. K. Lederhendler, & D. Minecke (Eds.), Advancing re-
search on developmental plasticity: Integrating the behavioral sciences
and the neurosciences of mental health (pp. 256). Bethesda, MD: Na-
tional Institutes of Mental Health.
Higuchi, T., Honda, K., Takano, S., & Negoro, H. (1988). Reduced oxy-
tocin response to osmotic stimulus and immobilization stress in lac-
tating rats. Journal of Endocrinology, 116(2), 225–230.
Hillbrand, M., & Spitz, R. T. (1999). Cholesterol and aggression. Aggres-
sion and Violent Behavior, 4(3), 359–370.
Hillbrand, M., Waite, B. M., Miller, D. S., Spitz, R. T., & Lingswiler,
V. M. (2000). Serum cholesterol concentrations and mood states in
violent psychiatric patients: An experience sampling study. Journal of
Behavioral Medicine, 23(6), 519–529.
Hoff, E. (2003). The specificity of environmental inf luence: Socioeco-
nomic status affects early vocabulary development via maternal
speech. Child Development, 74(5), 1368–1378.
House, J. S., Lepkowski, J. M., Kinney, A. M., Mero, R. P., Kessler, R. C.,
& Herzog, A. R. (1994). The social stratification of aging and health.
Journal of Health and Social Behavior, 35(3), 213–234.
Huether, G. (1998). Stress and the adaptive self-organization of neuronal
connectivity during early childhood. International Journal of Devel-
opmental Neuroscience, 16(3/4), 297–306.
Hughes, C., Deater-Deckard, K., & Cutting, A. L. (1999). Speak
roughly to your little boy? Sex differences in the relations between
parenting and preschoolers’ understanding of mind. Social Develop-
ment, 8(2), 143–160.
Hutton, J. L., Pharoah, P. O., Cooke, R. W., & Stevenson, R. C. (1997).
Differential effects of preterm birth and small gestational age on
cognitive and motor development. Archives of Disease in Childhood:
Fetal and Neonatal Edition, 76(2), F75–F81.
Inglis, G. C., Ingram, M. C., Holloway, C. D., Swan, L., Birnie, D., Hillis,
W. S., et al. (1999). Familial pattern of corticosteroids and their me-
tabolism in adult human subjects: The Scottish Adult Twin Study. Jour-
nal of Clinical Endocrinology and Metabolism, 84(11), 4132–4137.
Ishikawa, S. S., Raine, A., Lencz, T., Bihrle, S., & LaCasse, L. (2001).
Increased height and bulk in antisocial personality disorder and its
subtypes. Psychiatry Research, 105(3), 211–219.
Jackson, A. P., Brooks-Gunn, J., Huang, C. C., & Glassman, M. (2000).
Single mothers in low-wage jobs: Financial strain, parenting, and
preschoolers’ outcomes. Child Development, 71(5), 1409–1423.

Jacobson, L., & Sapolsky, R. (1991). The role of the hippocampus in
feedback regulation of the hypothalamic-pituitary-adrenocortical
axis. Endocrine Reviews, 12(2), 118–134.
James, G. D., Cates, E. M., Pickering, T. G., & Laragh, J. H. (1989). Parity
and perceived job stress elevate blood pressure in young normotensive
working women. American Journal of Hypertension, 2(8), 637–639.
Kagan, J., Reznick, J. S., & Snidman, N. (1987). The physiology and psy-
chology of behavioral inhibition in children. Child Development,
58(6), 1459–1473.
Kanemura, H., Aihara, M., Aoki, S., Hatakeyama, K., Kamiya, Y., Ono,
C., et al. (1999). Quantitative measurement of prefrontal lobe volume
on three-dimensional magnetic resonance imaging scan. Brain and
Development, 31(6), 519–524.
Kaplan, J. R., Shively, C. A., Fontenot, M. B., Morgan, T. M., Howell, S.
M., Manuck, S. B., et al. (1994). Demonstration of an association
among dietary cholesterol, central serotonergic activity, and social
behavior in monkeys. Psychosomatic Medicine, 56(6), 479–484.
Karlamangla, A. S., Singer, B. H., McEwen, B. S., Rowe, J. W., & See-
man, T. E. (2002). Allostatic load as a predictor of functional de-
cline: MacArthur studies of successful aging. Journal of Clinical
Epidemiology, 55(7), 696–710.
Kaufman, J., Birmaher, B., Perel, J., Dahl, R. E., Moreci, P., Nelson, B.,
et al. (1997). The corticotropin-releasing hormone challenge in de-
pressed abused, depressed nonabused, and normal control children.
Biological Psychiatry, 42(8), 669–679.
Kempermann, G., Kuhn, H. G., & Gage, F. H. (1997). More hippocampal
neurons in adult mice living in an enriched environment. Nature,
386(6624), 493–495.
Kiecolt-Glaser, J. K., Glaser, R., Gravenstein, S., Malarkey, W. B., &
Sheridan, J. (1996). Chronic stress alters the immune response to in-
f luenza virus vaccine in older adults. Proceedings of the National Acad-
emy of Sciences of the United States of America, 93(7), 3043–3047.
Kiehl, K. A., Smith, A. M., Hare, R. D., Mendrek, A., Forster, B. B.,
Brink, J., et al. (2001). Limbic abnormalities in affective processing
by criminal psychopaths as revealed by functional magnetic reso-
nance imaging. Biological Psychiatry, 50, 677–684.
Kindlon, D. J., Tremblay, R. E., Mezzacappa, E., Earls, F., Laurent, D., &
Schaal, B. (1995). Longitudinal patterns of heart rate and fighting
behavior in 9- through 12-year-old boys. Journal of the American
Academy of Child and Adolescent Psychiatry, 34(3), 371–377.
King, J. A., Barkley, R. A., & Barrett, S. (1998). Attention-deficit hyper-
activity disorder and the stress response. Biological Psychiatry,
44(1), 72–74.
Kirschbaum, C., & Hellhammer, D. (1989). Response variability of sali-
vary cortisol under psychological stimulation. Journal of Clinical
Chemistry and Clinical Biochemistry, 27(4), 237.
Kirschbaum, C., Klauer, T., Filipp, S. H., & Hellhammer, D. H. (1995).
Sex-specific effects of social support on cortisol and subjective re-
sponses to acute psychological stress. Psychosomatic Medicine,
57(1), 23–31.
Kirschbaum, C., Kudielka, B. M., Gaab, J., Schommer, N. C., & Hellham-
mer, D. H. (1999). Impact of gender, menstrual cycle phase, and oral
contraceptives on the activity of the hypothalamus-pituitary-adrenal
axis. Psychosomatic Medicine, 61(2), 154–162.
Kirschbaum, C., Prussner, J. C., Stone, A. A., Federenko, I., Gaab, J.,
Lintz, D., et al. (1995). Persistent high cortisol responses to repeated
psychological stress in a subpopulation of healthy men. Psychoso-
matic Medicine, 57(5), 468–474.
Kirschbaum, C., Wüst, S., Faig, H. G., & Hellhammer, D. H. (1992). Her-
itability of cortisol responses to human corticotropin-releasing hor-
mone, ergometry, and psychological stress in humans. Journal of
Clinical Endocrinology and Metabolism, 75(6), 1526–1530.
References 621
Krishnan, K. R., Doraiswamy, P. M., Figiel, G. S., Husain, M. M., Shah,
S. A., Na, C., et al. (1991). Hippocampal abnormalities in depression.
Journal of Neuropsychiatry and Clinical Neurosciences, 3(4), 387–391.
Kruesi, M. J., Casanova, M. F., Mannheim, G., & Johnson-Bilder, A.
(2004). Reduced temporal lobe volume in early onset conduct disor-
der. Psychiatry Research, 132, 1–11.
Kruesi, M. J., Schmidt, M. E., Donnelly, M., Hibbs, E. D., & Hamburger,
S. D. (1989). Urinary free cortisol output and disruptive behavior in
children. Journal of the American Academy of Child and Adolescent
Psychiatry, 28(3), 441–443.
Kudielka, B. M., Buske-Kirschbaum, A., Hellhammer, D. H., &
Kirschbaum, C. (2004). HPA axis responses to laboratory psychoso-
cial stress in healthy elderly adults, younger adults, and children: Im-
pact of age and gender. Psychoneuroendocrinology, 29(1), 83–98.
Kudielka, B. M., Schommer, N. C., Hellhammer, D. H., & Kirschbaum, C.
(2004). Acute HPA axis responses, heart rate, and mood changes to
psychosocial stress (TSST) in humans at different times of day. Psy-
choneuroendocrinology, 29(8), 983–992.
Kuenzel, W. J., Beck, M. M., & Teruyama, R. (1999). Neural sites and path-
ways regulating food intake in birds: A comparative analysis to mam-
malian systems. Journal of Experimental Zoology, 283(4/5), 348–364.
Kunz-Ebrecht, S. R., Kirschbaum, C., & Steptoe, A. (2004). Work stress,
socioeconomic status and neuroendocrine activation over the work-
ing day. Social Science and Medicine, 58(8), 1523–1530.
Lagercrantz, H. (1997). Better born too soon than too small. Lancet,
350(9084), 1044–1045.
Lahey, B. B., McBurnett, K., Loeber, R., & Hart, E. L. (1995). Psychobi-
ology. In G. Sholevar (Ed.), Conduct disorders in children and adoles-
cents (pp. 27–44). Washington, DC: American Psychiatric Press.
Landry, S. H., Smith, K. E., Miller-Loncar, C. L., & Swank, P. R. (1997).
Predicting cognitive-language and social growth curves from early
maternal behaviors in children at varying degrees of biological risk.
Developmental Psychology, 33(6), 1040–1053.
Laplante, D. P., Barr, R. G., Brunet, A., Galbaud du Fort, G., Meaney, M.
L., Saucier, J. F., et al. (2004). Stress during pregnancy affects gen-
eral intellectual and language functioning in human toddlers. Pedi-
atric Research, 56(3), 400–410.
LeDoux, J. E. (2003). The emotional brain, fear, and the amygdala. Cel-
lular and Molecular Neurobiology, 23(4/5), 727–738.
Leibowitz, S. F., & Hoebel, B. G. (1997). Behavioral neuroscience of
obesity. In G. A. Bray, C. Bouchard, & W. P. T. James (Eds.), Hand-
book of obesity (pp. 313–358). New York: Marcel Dekker.
Lemaire, V., Koehl, M., Le Moal, M., & Abrous, D. N. (2000). Prenatal
stress produces learning deficits associated with an inhibition of neu-
rogenesis in the hippocampus. Proceedings of the National Academy
of Sciences of the United States of America, 97(20), 11032–11037.
Lempers, J. D., Clark-Lempers, D., & Simons, R. L. (1989). Economic
hardship, parenting, and distress in adolescence. Child Development,
60(1), 25–39.
Lentjes, E. G., Griep, E. N., Boersma, J. W., Romijn, F. P., & de Kloet, E.
R. (1997). Glucocorticoid receptors, fibromyalgia and low back pain.
Psychoneuroendocrinology, 22(8), 603–614.
Leproult, R., Copinschi, G., Buxton, O., & Van Cauter, E. (1997). Sleep
loss results in an elevation of cortisol levels the next evening. Sleep,
20(10), 865–870.
Lesage, J., Blondeau, B., Grino, M., Breant, B., & Dupouy, J. P. (2001).
Maternal undernutrition during late gestation induces fetal overexpo-
sure to glucocorticoids and intrauterine growth retardation, and dis-
turbs the hypothalamo-pituitary-adrenal axis in the newborn rat.
Endocrinology, 142(5), 1692–1702.
622 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
Levine, S. (1994). The ontogeny of the hypothalamic-pituitary-adrenal
axis: The inf luence of maternal factors. Annals of the New York Acad-
emy of Sciences, 746, 275–293.
Levitt, N. S., Lindsay, R. S., Holmes, M. C., & Seckl, J. R. (1996). Dex-
amethasone in the last week of pregnancy attenuates hippocampal
glucocorticoid receptor gene expression and elevates blood pressure
in the adult offspring in the rat. Neuroendocrinology, 64(6), 412–418.
Lightman, S. L., & Young, W. S., III. (1989). Lactation inhibits stress-
mediated secretion of corticosterone and oxytocin and hypothalamic
accumulation of corticotropin-releasing factor and enkephalin mes-
senger ribonucleic acids. Endocrinology, 124(5), 2358–2364.
Lindberg, G., Rastam, L., Gullberg, B., & Eklund, G. A. (1992). Low
serum cholesterol concentration and short term mortality from injuries
in men and women. British Medical Journal, 305(6848), 277–279.
Ling, M. H., Perry, P. J., & Tsuang, M. T. (1981). Side effects of corti-
costeroid therapy: Psychiatric aspects. Archives of General Psychia-
try, 38(4), 471–477.
Lingas, R., Dean, F., & Matthews, S. G. (1999). Maternal nutrient re-
striction (48 h) modifies brain corticosteroid receptor expression
and endocrine function in the fetal guinea pig. Brain Research,
846(2), 236–242.
Linkowski, P., Van Onderbergen, A., Kerkhofs, M., Bosson, D.,
Mendlewicz, J., & Van Cauter, E. (1993). Twin study of the 24-h cor-
tisol profile: Evidence for genetic control of the human circadian
clock. American Journal of Physiology, 264(2, Pt. 1), E173–E181.
Linnoila, V. M., & Virkkunen, M. (1992). Aggression, suicidality, and
serotonin. Journal of Clinical Psychiatry, 53(Suppl.), 46–51.
Lundberg, U. (1996). Inf luence of paid and unpaid work on psychophysi-
ological stress responses of men and women. Journal of Occupational
Health Psychology, 1(2), 117–130.
Lupien, S. J., de Leon, M., de Santi, S., Convit, A., Tarshish, C., Nair, N.
P., et al. (1998). Cortisol levels during human aging predict hippocam-
pal atrophy and memory deficits. Nature Neuroscience, 1(1), 69–73.
Lupien, S. J., Fiocco, A., Wan, N., Maheu, F., Lord, C., Schramek, T.,
et al. (2005). Stress hormones and human memory function across the
lifespan. Psychoneuroendocrinology, 30(3), 225–242.
Lupien, S. J., Gaudreau, S., Tchiteya, B. M., Maheu, F., Sharma, S., Nair,
N. P., et al. (1997). Stress-induced declarative memory impairment in
healthy elderly subjects: Relationship to cortisol reactivity. Journal
of Clinical Endocrinology and Metabolism, 82(7), 2070–2075.
Lupien, S. J., King, S., Meaney, M. J., & McEwen, B. S. (2000). Child’s
stress hormone levels correlate with mother’s socioeconomic status
and depressive state. Biological Psychiatry, 48(10), 976–980.
Lupien, S. J., King, S., Meaney, M. J., & McEwen, B. S. (2001). Can
poverty get under your skin? Basal cortisol levels and cognitive func-
tion in children from low and high socioeconomic status. Develop-
ment and Psychopathology, 13, 651–674.
Lupien, S. J., Lecours, A. R., Lussier, I., Schwartz, G., Nair, N. P., &
Meaney, M. J. (1994). Basal cortisol levels and cognitive deficits in
human aging. Journal of Neuroscience, 14(5, Pt. 1), 2893–2903.
Lupien, S. J., Lecours, A. R., Schwartz, G., Sharma, S., Hauger, R. L.,
Meaney, M. J., et al. (1996). Longitudinal study of basal cortisol lev-
els in healthy elderly subjects: Evidence for subgroups. Neurobiology
of Aging, 17(1), 95–105.
Lupien, S. J., & Lepage, M. (2001). Stress, memory, and the hippocam-
pus: Can’t live with it, can’t live without it. Behavioral Brain Re-
search, 127(1/2), 137–158.
Lupien, S. J., & McEwen, B. S. (1997). The acute effects of corticos-
teroids on cognition: Integration of animal and human model studies.
Brain Research Reviews, 24(1), 1–27.
Luthar, S. S. (2003). Resilience and vulnerability: Adaptation in the con-
text of childhood adversities. Cambridge, England: Cambridge Uni-
versity Press.
Maguire, E. A., Gadian, D. G., Johnsrude, I. S., Good, C. D., Ashburner, J.,
Frackowiak, R. S., et al. (2000). Navigation-related structural change
in the hippocampi of taxi drivers. Proceedings of the National Academy
of Sciences of the United States of America, 97(8), 4398–4403.
Maheu, F. S., Joober, R., Beaulieu, S., & Lupien, S. J. (2004). Differen-
tial effects of adrenergic and corticosteroid hormonal systems on
human short- and long-term declarative memory for emotionally
arousing material. Behavioral Neuroscience, 118(2), 420–428.
Maheu, F. S., & Lupien, S. J. (2003). Memory in the grip of emotions
and stress: A necessarily harmful impact. Medicine Sciences,
19(1), 118–124.
Mahon, T. R., Chazotte, C., & Cohen, W. R. (1994). Short labor: Charac-
teristics and outcome. Obstetrics and Gynecology, 84(1), 47–51.
Markowe, H. L., Marmot, M. G., Shipley, M. J., Bulpitt, C. J., Meade, T.
W., Stirling, Y., et al. (1985). Fibrinogen: A possible link between so-
cial class and coronary heart disease. British Medical Journal,
291(6505), 1312–1314.
Martyn, C. N., Gale, C. R., Sayer, A. A., & Fall, C. (1996). Growth in utero
and cognitive function in adult life: Follow up study of people born be-
tween 1920 and 1943. British Medical Journal, 312(7043), 1393–1396.
Mason, J. W. (1968). A review of psychoendocrine research on the sym-
pathetic-adrenal medullary system. Psychosomatic Medicine, 30(5,
Suppl.), 631–653.
Masten, A. S. (2001). Ordinary magic: Resilience processes in develop-
ment. American Psychologist, 56(3), 227–238.
Masten, A. S., Hubbard, J. J., Gest, S. D., Tellegen, A., Garmezy, N., &
Ramirez, M. (1999). Competence in the context of adversity: Path-
ways to resilience and maladaptation from childhood to late adoles-
cence. Development and Psychopathology, 11(1), 143–169.
Matsuzawa, J., Matsui, M., Konishi, T., Noguchi, K., Gur, R. C., Bilker,
W., et al. (2001). Age-related volumetric changes of brain gray and
white matter in healthy infants and children. Cerebral Cortex,
11(4), 335–342.
May, M., Holmes, E., Rogers, W., & Poth, M. (1990). Protection from
glucocorticoid induced thymic involution by dehydroepiandrosterone.
Life Sciences, 46(22), 1627–1631.
McBurnett, K., & Lahey, B. B. (1994). Psychophysiological and neuroen-
docrine correlates of conduct disorder and antisocial behavior in chil-
dren and adolescents. Progress in Experimental Personality and
Psychopathology Research, 199–231.
McBurnett, K., Lahey, B. B., Capasso, L., & Loeber, R. (1996). Aggressive
symptoms and salivary cortisol in clinic-referred boys with conduct
disorder. Annals of the New York Academy of Sciences, 794, 169–178.
McBurnett, K., Lahey, B. B., Frick, P. J., Risch, C., Loeber, R., Hart, E.
L., et al. (1991). Anxiety, inhibition, and conduct disorder in chil-
dren: II. Relation to salivary cortisol. Journal of the American Acad-
emy of Child and Adolescent Psychiatry, 30(2), 192–196.
McBurnett, K., Lahey, B. B., Rathouz, P. J., & Loeber, R. (2000). Low
salivary cortisol and persistent aggression in boys referred for dis-
ruptive behavior. Archives of General Psychiatry, 57(1), 38–43.
McEwen, B. S. (1998a). Protective and damaging effects of stress medi-
ators. New England Journal of Medicine, 338(3), 171–179.
McEwen, B. S. (1998b). Stress, adaptation, and disease: Allostasis and al-
lostatic load. Annals of the New York Academy of Sciences, 840, 33–44.
McEwen, B. S. (2000a). Allostasis and allostatic load: Implications for neu-
ropsychopharmacology. Neuropsychopharmacology, 22(2), 108–124.
McEwen, B. S. (2000b). The neurobiology of stress: From serendipity to
clinical relevance. Brain Research, 886(1/2), 172–189.

McEwen, B. S. (2002). Protective and damaging effects of stress media-
tors: The good and bad sides of the response to stress. Metabolism,
51(6, Suppl. 1), 2–4.
McEwen, B. S. (2003). Mood disorders and allostatic load. Biological
Psychiatry, 54(3), 200–207.
McEwen, B. S., & Seeman, T. (1999). Protective and damaging effects
of mediators of stress: Elaborating and testing the concepts of al-
lostasis and allostatic load. Annals of the New York Academy of Sci-
ences, 896, 30–47.
McEwen, B. S., & Stellar, E. (1993). Stress and the individual: Mechanisms
leading to disease. Archives of Internal Medicine, 153(18), 2093–2101.
McEwen, B. S., & Wingfield, J. C. (2003). The concept of allostasis in
biology and biomedicine. Hormones and Behavior, 43(1), 2–15.
McGaugh, J. L. (2000). Memory: A century of consolidation. Science,
287(5451), 248–251.
McLean, M., Bisits, A., Davies, J., Woods, R., Lowry, P., & Smith, R.
(1995). A placental clock controlling the length of human pregnancy.
Nature Medicine, 1(5), 460–463.
McLeod, J. D., & Kessler, R. C. (1990). Socioeconomic status differ-
ences in vulnerability to undesirable life events. Journal of Health
and Social Behavior, 31(2), 162–172.
McLeod, J. D., & Nonnemaker, J. M. (2000). Poverty and child emotional
and behavioral problems: Racial /ethnic differences in processes and
effects. Journal of Health and Social Behavior, 41, 137–161.
McLeod, J. D., & Shanahan, M. J. (1993). Poverty, parenting, and chil-
dren’s mental health. American Sociological Review, 58(3), 351–366.
McLoyd, V. C. (1998). Socioeconomic disadvantage and child develop-
ment. American Psychologist, 53(2), 185–204.
Meaney, M. J. (2001). Maternal care, gene expression, and the transmis-
sion of individual differences in stress reactivity across generations.
Annual Review of Neuroscience, 24, 1161–1192.
Meaney, M. J., Aitken, D. H., Viau, V., Sharma, S., & Sarrieau, A.
(1989). Neonatal handling alters adrenocortical negative feedback
sensitivity and hippocampal type II glucocorticoid receptor binding
in the rat. Neuroendocrinology, 50(5), 597–604.
Meaney, M. J., Diorio, J., Francis, D., Widdowson, J., LaPlante, P.,
Caldji, C., et al. (1996). Early environmental regulation of forebrain
glucocorticoid receptor gene expression: Implications for adrenocor-
tical responses to stress. Developmental Neuroscience, 18(1/2), 49–72.
Meaney, M. J., Mitchell, J. B., Aitken, D. H., Bhatnager, J., Bodnoff, S.
R., Iny, L. J., et al. (1991). The effects of neonatal handling on the
development of the adrenocortical response to stress: Implications for
neuropathology and cognitive deficits in later life. Psychoneuroen-
docrinology, 16, 85–103.
Meeran, K., Hattersley, A., Mould, G., & Bloom, S. R. (1993). Venepunc-
ture causes rapid rise in plasma ACTH. British Journal of Clinical
Practice, 47(5), 246–247.
Meikle, A. W., Stringham, J. D., Woodward, M. G., & Bishop, D. T.
(1988). Heritability of variation of plasma cortisol levels. Metabo-
lism, 37(6), 514–517.
Menard, J. L., Champagne, D. L., & Meaney, M. J. (2004). Variations of
maternal care differentially inf luence “ fear ” reactivity and regional
patterns of cFos immunoreactivity in response to the shock-probe
burying test. Neuroscience, 129(2), 297–308.
Michelson, D., Stratakis, C., Hill, L., Reynolds, J., Galliven, E.,
Chrousos, G., et al. (1996). Bone mineral density in women with de-
pression. New England Journal of Medicine, 335(16), 1176–1181.
Milburn, H. J., Poulter, L. W., Dilmec, A., Cochrane, G. M., & Kemeny,
D. M. (1997). Corticosteroids restore the balance between locally
produced Th1 and Th2 cytokines and immunoglobulin isotypes to
References 623
normal in sarcoid lung. Clinical and Experimental Immunology,
108(1), 105–113.
Miller, L. S., Wasserman, G. A., Neugebauer, R., Gorman-Smith, D., &
Kamboukos, D. (1999). Witnessed community violence and antisocial
behavior in high-risk, urban boys. Journal of Clinical Child Psychol-
ogy, 28(1), 2–11.
Miner, J. N., Diamond, M. I., & Yamamoto, K. R. (1991). Joints in the
regulatory lattice: Composite regulation by steroid receptor-AP1
complexes. Cell Growth and Dif ferentiation, 2(10), 525–530.
Ming, E. E., Adler, G. K., Kessler, R. C., Fogg, L. F., Matthews, K. A.,
Herd, J. A., et al. (2004). Cardiovascular reactivity to work stress
predicts subsequent onset of hypertension: The Air Traffic Controller
Health Change Study. Psychosomatic Medicine, 66(4), 459–465.
Moffitt, T. E., Caspi, A., Harrington, H., & Milner, B. J. (2002). Males
on the life-course-persistent and adolescence-limited antisocial path-
ways: Follow-up at age 26 years. Development and Psychopathology,
14, 179–207.
Morales, A. J., Nolan, J. J., Nelson, J. C., & Yen, S. S. (1994). Effects of
replacement dose of dehydroepiandrosterone in men and women of
advancing age. Journal of Clinical Endocrinology and Metabolism,
78(6), 1360–1367.
Muldoon, M. F., Manuck, S. B., & Matthews, K. A. (1990). Lowering cho-
lesterol concentrations and mortality: A quantitative review of pri-
mary prevention trials. British Medical Journal, 301(6747), 309–314.
Murray, L., Woolgar, M., Briers, S., & Hipwell, A. (1999). Children’s so-
cial representations in dolls’ house play and theory of mind tasks, and
their relation to family adversity and child disturbance. Social Devel-
opment, 8(2), 179–200.
Mustillo, S., Worthman, C., Erkanli, A., Keeler, G., Angold, A., &
Costello, E. J. (2003). Obesity and psychiatric disorder: Developmen-
tal trajectories. Pediatrics, 111(4, Pt. 1), 851–859.
Mysterud, I., & Poleszynski, D. V. (2003). Expanding evolutionary psy-
chology: Toward a better understanding of violence and aggression.
Social Science Information, 23, 5–50.
Neale, M. C., & Cardon, L. R. (1992). Methodology for genetic studies of
twins and families. Dordrecht, The Netherlands: Kluwer Academic.
Nelson, M. D., Saykin, A. J., Flashman, L. A., & Riordan, H. J. (1998).
Hippocampal volume reduction in Schizophrenia as assessed by mag-
netic resonance imaging: A meta-analytic study. Archives of General
Psychiatry, 55(5), 433–440.
Neumann, I. D., Johnstone, H. A., Hatzinger, M., Liebsch, G., Shipston,
M., Russell, J. A., et al. (1998). Attenuated neuroendocrine responses
to emotional and physical stressors in pregnant rats involve adenohy-
pophysial changes. Journal of Physiology, 508(Pt. 1), 289–300.
Neumann, I. D., Russell, J. A., & Landgraf, R. (1993). Oxytocin and va-
sopressin release within the supraoptic and paraventricular nuclei of
pregnant, parturient and lactating rats: A microdialysis study. Neuro-
science, 53(1), 65–75.
Neumann, I. D., Toschi, N., Ohl, F., Torner, L., & Kromer, S. A. (2001).
Maternal defense as an emotional stressor in female rats: Correlation
of neuroendocrine and behavioural parameters and involvement of
brain oxytocin. European Journal of Neuroscience, 13(5), 1016–1024.
Newman, R. B., Goldenberg, R. L., Moawad, A. H., Iams, J. D., Meis, P.
J., Das, A., et al. (2001). Occupational fatigue and preterm premature
rupture of membranes: National Institute of Child Health and Human
Development Maternal-Fetal Medicine Units Network. American
Journal of Obstetrics and Gynecology, 184(3), 438–446.
Nurnberger, J. I., Jr., Gershon, E. S., Simmons, S., Ebert, M., Kessler,
L. R., Dibble, E. D., et al. (1982). Behavioral, biochemical and neu-
roendocrine responses to amphetamine in normal twins and “ well-
state” bipolar patients. Psychoneuroendocrinology, 7(2/3), 163–176.
624 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
Orentreich, N., Brind, J. L., Rizer, R. L., & Vogelman, J. H. (1984). Age
changes and sex differences in serum dehydroepiandrosterone sulfate
concentrations throughout adulthood. Journal of Clinical Endocrinol-
ogy and Metabolism, 59(3), 551–555.
Ortiz, J., & Raine, A. (2004). Heart rate level and antisocial behavior in
children and adolescents: A meta-analysis. Journal of the American
Academy of Child and Adolescent Psychiatry, 43(2), 154–162.
Owen, A. M., Doyon, J., Petrides, M., & Evans, A. C. (1996). Planning
and spatial working memory: A positron emission tomography study
in humans. European Journal of Neuroscience, 8, 353–364.
Paarlberg, K. M., Vingerhoets, A. J., Passchier, J., Dekker, G. A., & Van
Geijn, H. P. (1995). Psychosocial factors and pregnancy outcome: A
review with emphasis on methodological issues. Journal of Psychoso-
matic Research, 39(5), 563–595.
Pajer, K., Gardner, W., Rubin, R. T., Perel, J., & Neal, S. (2001). De-
creased cortisol levels in adolescent girls with conduct disorder.
Archives of General Psychiatry, 58(3), 297–302.
Pajer, K., Rabin, B., & Gardner, W. (2002). Increased IgG 3, 4 ratios in
adolescent antisocial females: Evidence of Th1/ Th2 imbalance?
Brain, Behavior, and Immunity, 16(6), 747–756.
Patacchioli, F. R., Cigliana, G., Cilumbriello, A., Perrone, G., Capri, O.,
Alema, G. S., et al. (1992). Maternal plasma and milk free cortisol
during the first 3 days of breast-feeding following spontaneous deliv-
ery or elective cesarean section. Gynecologic and Obstetric Investiga-
tion, 34(3), 159–163.
Patrick, C. J., Cuthbert, B. N., & Lang, P. J. (1994). Emotion in the crim-
inal psychopath: Fear image processing. Journal of Abnormal Psy-
chology, 103, 523–534.
Peacock, J. L., Bland, J. M., & Anderson, H. R. (1995). Preterm delivery:
Effects of socioeconomic factors, psychological stress, smoking, al-
cohol, and caffeine. British Medical Journal, 311(7004), 531–535.
Pears, K. C., & Moses, L. J. (2003). Demographics, parenting, and theory
of mind in preschool children. Social Development, 12(1), 1–19.
Pfefferbaum, A., Mathalon, D. H., Sullivan, E. V., Rawles, J. M.,
Zipursky, R. B., & Lim, K. O. (1994). A quantitative magnetic reso-
nance imaging study of changes in brain morphology from infancy to
late adulthood. Archives of Neurology, 51(9), 874–887.
Phillips, D. I. (1998). Birth weight and the future development of diabetes:
A review of the evidence. Diabetes Care, 21(Suppl. 2), B150–B155.
Pickering, T. G. (1996a). Job strain and the prevalence and outcome of
coronary artery disease. Circulation, 94(5), 1138–1139.
Pickering, T. G. (1996b). White coat hypertension. Current Opinion in
Nephrology and Hypertension, 5(2), 192–198.
Pickering, T. G., Devereux, R. B., James, G. D., Gerin, W., Landsbergis,
P., Schnall, P. L., et al. (1996). Environmental inf luences on blood
pressure and the role of job strain. Journal of Hypertension, 14(5,
Suppl.), S179–S185.
Pinker, S. (1994). The language instinct. New York: Morrow.
Plomin, R., DeFries, J. C., McClearn, G. E., & McGuffin, P. (2001). Be-
havioral genetics (4th ed.). New York: Worth.
Plotsky, P. M., & Meaney, M. J. (1993). Early, postnatal experience al-
ters hypothalamic corticotropin-releasing factor (CRF) mRNA, me-
dian eminence CRF content and stress-induced release in adult rats.
Brain Research. Molecular Brain Research, 18(3), 195–200.
Pollak, S. D., Cicchetti, D., Hornung, K., & Reed, A. (2000). Recogniz-
ing emotion in faces: Developmental effects of child abuse and neg-
lect. Developmental Psychology, 36(5), 679–688.
Pollak, S. D., & Kistler, D. J. (2002). Early experience is associated with
the development of categorical representations for facial expressions
of emotion. Proceedings of the National Academy of Sciences of the
United States of America, 99(13), 9072–9076.
Pollak, S. D., & Sinha, P. (2002). Effects of early experience on chil-
dren’s recognition of facial displays of emotion. Developmental Psy-
chology, 38(5), 784–791.
Pollak, S. D., & Tolley-Schell, S. A. (2003). Selective attention to facial
emotion in physically abused children. Journal of Abnormal Psychol-
ogy, 112(3), 323–338.
Posthuma, D., de Geus, E. J. C., Neale, M. C., Hulshoff Pol, H. E., Baaré,
W. F. C., Kahn, R. S., et al. (2000). Multivariate genetic analysis of
brain structure in an extended twin design. Behavior Genetics, 30,
311–319.
Pritchard, J., Despres, J. P., Gagnon, J., Tchernof, A., Nadeau, A., Trem-
blay, A., et al. (1998). Plasma adrenal, gonadal, and conjugated
steroids before and after long-term overfeeding in identical twins.
Journal of Clinical Endocrinology and Metabolism, 83(9), 3277–3284.
Pruessner, J. C., Hellhammer, D. H., & Kirschbaum, C. (1999). Burnout,
perceived stress, and cortisol responses to awakening. Psychosomatic
Medicine, 61(2), 197–204.
Pruessner, J. C., Wolf, O. T., Hellhammer, D. H., Buske-Kirschbaum, A.,
von Auer, K., Jobst, S., et al. (1997). Free cortisol levels after awak-
ening: A reliable biological marker for the assessment of adrenocorti-
cal activity. Life Sciences, 61(26), 2539–2549.
Pruessner, M., Hellhammer, D. H., Pruessner, J. C., & Lupien, S. J.
(2003). Self-reported depressive symptoms and stress levels in
healthy young men: Associations with the cortisol response to awak-
ening. Psychosomatic Medicine, 65(1), 92–99.
Rabin, B. S. (1999). Stress, immune function, and health: The connection.
New York: Wiley-Liss & Sons.
Raine, A. (1993). The psychopathology of crime: Criminal behavior as a
clinical disorder. Academic Press.
Raine, A., Lencz, T., Bihrle, S., LaCasse, L., & Colletti, P. (2000). Re-
duced prefrontal gray matter volume and reduced autonomic activity
in antisocial personality disorder. Archives of General Psychiatry,
57, 119–127.
Raine, A., Venables, P. H., & Mednick, S. A. (1997). Low resting heart
rate at age 3 years predisposes to aggression at age 11 years: Evi-
dence from the Mauritius Child Health Project. Journal of the Ameri-
can Academy of Child and Adolescent Psychiatry, 36(10), 1457–1464.
Raine, A., Venables, P. H., & Williams, M. (1995). High autonomic
arousal and electrodermal orienting at age 15 years as protective fac-
tors against criminal behavior at age 29 years. American Journal of
Psychiatry, 152(11), 1595–1600.
Reiss, A. L., Abrams, M. T., Singer, H. S., Ross, J. L., & Denckla, M. B.
(1996). Brain development, gender and IQ in children: A volumetric
imaging study. Brain, 119(Pt. 5), 1763–1774.
Repetti, R. L., Taylor, S. E., & Seeman, T. E. (2002). Risky families:
Family social environments and the mental and physical health of off-
spring. Psychological Bulletin, 128(2), 330–366.
Righetti-Veltema, M., Conne-Perreard, E., Bousquet, A., & Manzano, J.
(1998). Risk factors and predictive signs of postpartum depression.
Journal of Af fective Disorders, 49(3), 167–180.
Rini, C. K., Dunkel-Schetter, C., Wadhwa, P. D., & Sandman, C. A.
(1999). Psychological adaptation and birth outcomes: The role of per-
sonal resources, stress, and sociocultural context in pregnancy.
Health Psychology, 18(4), 333–345.
Robbins, J., Hirsch, C., Whitmer, R., Cauley, J., & Harris, T. (2001). The
association of bone mineral density and depression in an older popu-
lation. Journal of the American Geriatrics Society, 49(6), 732–736.
Robel, P., & Baulieu, E. E. (1995). Dehydroepiandrosterone (DHEA) is a
neuroactive neurosteroid. Annals of the New York Academy of Sci-
ences, 774, 82–110.

Rogers, C. R. (1951). Client-centered therapy. Boston: Houghton
Miff lin.
Rohleder, N., Wolf, J. M., & Kirschbaum, C. (2003). Glucocorticoid sen-
sitivity in humans: Interindividual differences and acute stress ef-
fects. Stress, 6(3), 207–222.
Roozendaal, B. (2000). 1999 Curt P. Richter Award: Glucocorticoids and
the regulation of memory consolidation. Psychoneuroendocrinology,
25(3), 213–238.
Roozendaal, B. (2003). Systems mediating acute glucocorticoid effects
on memory consolidation and retrieval. Progress in Neuropsychophar-
macology and Biological Psychiatry, 27(8), 1213–1223.
Roozendaal, B., Hahn, E. L., Nathan, S. V., de Quervain, D. J., & Mc-
Gaugh, J. L. (2004). Glucocorticoid effects on memory retrieval re-
quire concurrent noradrenergic activity in the hippocampus and
basolateral amygdala. Journal of Neuroscience, 24(37), 8161–8169.
Roozendaal, B., McReynolds, J. R., & McGaugh, J. L. (2004). The baso-
lateral amygdala interacts with the medial prefrontal cortex in regu-
lating glucocorticoid effects on working memory impairment.
Journal of Neuroscience, 24(6), 1385–1392.
Roy, M. P., Steptoe, A., & Kirschbaum, C. (1998). Life events and social
support as moderators of individual differences in cardiovascular and
cortisol reactivity. Journal of Personality and Social Psychology,
75(5), 1273–1281.
Rubinow, D. R., Post, R. M., Savard, R., & Gold, P. W. (1984). Cortisol
hypersecretion and cognitive impairment in depression. Archives of
General Psychiatry, 41(3), 279–283.
Russell, J. A., Douglas, A. J., & Ingram, C. D. (2001). Brain preparations
for maternity: Adaptive changes in behavioral and neuroendocrine
systems during pregnancy and lactation. An overview. Progress in
Brain Research, 133, 1–38.
Rutter, M. (1994). Stress research: Accomplishments and tasks ahead. In
R. J. Haggerty, L. R. Sherrod, N. Garmezy, & M. Rutter (Eds.),
Stress, risk, and resilience in children and adolescents: Processes,
mechanisms, and interventions (pp. 304–329). Cambridge, England:
Cambridge University Press.
Rutter, M., & Silberg, J. (2002). Gene-environment interplay in relation
to emotional and behavioral disturbance. Annual Review of Psychol-
ogy, 53, 463–490.
Sachar, E. J., Hellman, L., Roffwarg, H. P., Halpern, F. S., Fukushima, D.
K., & Gallagher, T. F. (1973). Disrupted 24-hour patterns of cortisol
secretion in psychotic depression. Archives of General Psychiatry,
28(1), 19–24.
Sammons, L. N. (1990). Psychological aspects of second pregnancy.
NAACOG’s Clinical Issues in Perinatal and Women’s Health Nursing,
1(3), 317–324.
Sandler, I. (2001). Quality and ecology of adversity as common mecha-
nisms of risk and resilience. American Journal of Community Psy-
chology, 29(1), 19–61.
Sapolsky, R. M., Krey, L. C., & McEwen, B. S. (1986). The neuroen-
docrinology of stress and aging: The glucocorticoid cascade hypothe-
sis. Endocrine Reviews, 7(3), 284–301.
Scarpa, A., & Ollendick, T. H. (2003). Community violence exposure in
a young adult sample: III. Psychophysiology and victimization inter-
act to affect risk for aggression. Journal of Community Psychology,
31(4), 321–338.
Scarpa, A., & Raine, A. (1997). Psychophysiology of anger and violent
behavior. Psychiatric Clinics of North America, 20(2), 375–394.
Schapiro, S., Geller, E., & Eiduson, S. (1962). Neonatal adrenal cortical
response to stress and vasopressin. Proceedings of the Society for Ex-
perimental Biology and Medicine, 109, 937–941.
References 625
Schieken, R. M., Eaves, L. J., Hewitt, J. K., Mosteller, M., Bodurtha, J.
N., Moskowitz, W. B., et al. (1989). Univariate genetic analysis of
blood pressure in children (the Medical College of Virginia Twin
Study). American Journal of Cardiology, 64(19), 1333–1337.
Schnorpfeil, P., Noll, A., Schulze, R., Ehlert, U., Frey, K., & Fischer,
J. E. (2003). Allostatic load and work conditions. Social Science and
Medicine, 57(4), 647–656.
Schoenbaum, G., Setlow, B., Saddoris, M. P., & Gallagher, M. (2003).
Encoding predicted outcome and acquired value in orbitofrontal cor-
tex during cue sampling depends upon input from basolateral amyg-
dala. Neuron, 39, 855–867.
Schulz, K. P., Halperin, J. M., Newcorn, J. H., Sharma, V., & Gabriel,
S. (1997). Plasma cortisol and aggression in boys with ADHD. Jour-
nal of the American Academy of Child and Adolescent Psychiatry,
36(5), 605–609.
Schulz, K. P., Kirschbaum, C., Pruessner, J. C., & Hellhammer, D.
(1998). Increased free cortisol secretion after awakening in chroni-
cally stressed individuals due to work overload. Stress Medicine,
14(2), 91–97.
Schwartz, J. E., Pickering, T. G., & Landsbergis, P. A. (1996). Work-re-
lated stress and blood pressure: Current theoretical models and con-
siderations from a behavioral medicine perspective. Journal of
Occupational Health Psychology, 1(3), 287–310.
Schwarzer, R., & Leppin, A. (1989). Social support and health: A meta-
analysis. Psychology and Health, 3(1), 1–15.
Scott, L. V., Medbak, S., & Dinan, T. G. (1998). Blunted adrenocorti-
cotropin and cortisol responses to corticotropin-releasing hormone
stimulation in chronic fatigue syndrome. Acta Psychiatrica Scandi-
navica, 97(6), 450–457.
Seckl, J. R., Cleasby, M., & Nyirenda, M. J. (2000). Glucocorticoids,
11beta-hydroxysteroid dehydrogenase, and fetal programming. Kid-
ney International, 57(4), 1412–1417.
Seeman, T. E., Charpentier, P. A., Berkman, L. F., Tinetti, M. E., Gural-
nik, J. M., Albert, M., et al. (1994). Predicting changes in physical
performance in a high-functioning elderly cohort: MacArthur studies
of successful aging. Journal of Gerontology, 49(3), M97–M108.
Seeman, T. E., & Chen, X. (2002). Risk and protective factors for physi-
cal functioning in older adults with and without chronic conditions:
MacArthur Studies of Successful Aging. Journals of Gerontology. Se-
ries B, Psychological Sciences and Social Sciences, 57(3), S135–S144.
Seeman, T. E., Crimmins, E., Huang, M. H., Singer, B., Bucur, A., Grue-
newald, T., et al. (2004). Cumulative biological risk and socio-eco-
nomic differences in mortality: MacArthur studies of successful
aging. Social Science and Medicine, 58(10), 1985–1997.
Seeman, T. E., Glei, D., Goldman, N., Weinstein, M., Singer, B., & Lin,
Y. H. (2004). Social relationships and allostatic load in Taiwanese el-
derly and near elderly. Social Science and Medicine, 59(11),
2245–2257.
Seeman, T. E., Lusignolo, T. M., Albert, M., & Berkman, L. (2001). So-
cial relationships, social support, and patterns of cognitive aging in
healthy, high-functioning older adults: MacArthur studies of success-
ful aging. Health Psychology, 20(4), 243–255.
Seeman, T. E., McEwen, B. S., Rowe, J. W., & Singer, B. H. (2001). Allo-
static load as a marker of cumulative biological risk: MacArthur
studies of successful aging. Proceedings of the National Academy of
Sciences of the United States of America, 98(8), 4770–4775.
Seeman, T. E., Singer, B. H., Rowe, J. W., Horwitz, R. I., & McEwen,
B. S. (1997). Price of adaptation: Allostatic load and its health con-
sequences: MacArthur studies of successful aging. Archives of Inter-
nal Medicine, 157(19), 2259–2268.
626 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
Seeman, T. E., Singer, B. H., Ryff, C. D., Dienberg Love, G., & Levy-
Storms, L. (2002). Social relationships, gender, and allostatic load
across two age cohorts. Psychosomatic Medicine, 64(3), 395–406.
Seidman, D. S., Laor, A., Gale, R., Stevenson, D. K., Mashiach, S., &
Danon, Y. L. (1992). Birth weight and intellectual performance in
late adolescence. Obstetrics and Gynecology, 79(4), 543–546.
Selye, H. (1975a). Confusion and controversy in the stress field. Journal
of Human Stress, 1(2), 37–44.
Selye, H. (1975b). Stress and distress. Comprehensive Therapy, 1(8), 9–13.
Selye, H. (1998). A syndrome produced by diverse nocuous agents: 1936.
Journal of Neuropsychiatry and Clinical Neurosciences, 10(2), 230–231.
Sgoifo, A., de Boer, S. F., Haller, J., & Koolhaas, J. M. (1996). Individual
differences in plasma catecholamine and corticosterone stress re-
sponses of wild-type rats: Relationship with aggression. Physiology
and Behavior, 60(6), 1403–1407.
Shanks, N., Windle, R. J., Perks, P., Wood, S., Ingram, C. D., & Light-
man, S. L. (1999). The hypothalamic-pituitary-adrenal axis response
to endotoxin is attenuated during lactation. Journal of Neuroen-
docrinology, 11(11), 857–865.
Sheline, Y. I. (1996). Hippocampal atrophy in major depression: A re-
sult of depression-induced neurotoxicity? Molecular Psychiatry,
1(4), 298–299.
Sheline, Y. I., Gado, M. H., & Kraemer, H. C. (2003). Untreated depres-
sion and hippocampal volume loss. American Journal of Psychiatry,
160(8), 1516–1518.
Sheline, Y. I., Sanghavi, M., Mintun, M. A., & Gado, M. H. (1999). De-
pression duration but not age predicts hippocampal volume loss in
medically healthy women with recurrent major depression. Journal of
Neuroscience, 19(12), 5034–5043.
Sheline, Y. I., Wang, P. W., Gado, M. H., Csernansky, J. G., & Vannier,
M. W. (1996). Hippocampal atrophy in recurrent major depression.
Proceedings of the National Academy of Sciences of the United States
of America, 93(9), 3908–3913.
Shors, T. J., Miesegaes, G., Beylin, A., Zhao, M., Rydel, T., & Gould, E.
(2001). Neurogenesis in the adult is involved in the formation of trace
memories. Nature, 410(6826), 372–376.
Shurin, M. R., Lu, L., Kalinski, P., Stewart-Akers, A. M., & Lotze, M. T.
(1999). Th1/ Th2 balance in cancer, transplantation and pregnancy.
Springer Seminars in Immunopathology, 21(3), 339–359.
Siegel, G. J., Agranoff, B. W., Albers, R. W., Fisher, S. K., & Uhler,
M. D. (1999). Basic neurochemistry. New York: Lippincott-Raven.
Singer, B., & Ryff, C. D. (1999). Hierarchies of life histories and asso-
ciated health risks. Annals of the New York Academy of Sciences,
896, 96–115.
Snoek, H., Van Goozen, S. H., Matthys, W., Buitelaar, J. K., & van Enge-
land, H. (2004). Stress responsivity in children with externalizing be-
havior disorders. Development and Psychopathology, 16(2), 389–406.
Somes, G. W., Harshfield, G. A., Alpert, B. S., Goble, M. M., &
Schieken, R. M. (1995). Genetic inf luences on ambulatory blood
pressure patterns: The Medical College of Virginia Twin Study.
American Journal of Hypertension, 8(5, Pt. 1), 474–478.
Sowell, E. R., Thompson, P. M., Tessner, K. D., & Toga, A. W. (2001).
Mapping continued brain growth and gray matter density reduction in
dorsal frontal cortex: Inverse relationships during postadolescent
brain maturation. Journal of Neuroscience, 21(22), 8819–8829.
Spangler, G., & Grossmann, K. E. (1993). Biobehavioral organization
in securely and insecurely attached infants. Child Development,
64(5), 1439–1450.
Spoont, M. R. (1992). Modulatory role of serotonin in neural information
processing: Implications for human psychopathology. Psychological
Bulletin, 112(2), 330–350.
Sprietsma, J. E. (1999). Modern diets and diseases: NO-zinc balance—
Under Th1, zinc and nitrogen monoxide (NO) collectively protect
against viruses, AIDS, autoimmunity, diabetes, allergies, asthma, in-
fectious diseases, atherosclerosis and cancer. Medical Hypotheses,
53(1), 6–16.
Stansbury, K., & Harris, M. L. (2000). Individual differences in stress
reactions during a peer entry episode: Effects of age, temperament,
approach behavior, and self-perceived peer competence. Journal of
Experimental Child Psychology, 76(1), 50–63.
Starf ield, E. L. (1982). Child health and social status. Pediatrics,
69, 550 –557.
Starkman, M. N., Gebarski, S. S., Berent, S., & Schteingart, D. E.
(1992). Hippocampal formation volume, memory dysfunction, and
cortisol levels in patients with Cushing’s syndrome. Biological Psy-
chiatry, 32(9), 756–765.
Starkman, M. N., Giordani, B., Berent, S., Schork, M. A., & Schtein-
gart, D. E. (2001). Elevated cortisol levels in Cushing’s disease are
associated with cognitive decrements. Psychosomatic Medicine,
63(6), 985–993.
Starkman, M. N., Giordani, B., Gebarski, S. S., Berent, S., Schork, M.
A., & Schteingart, D. E. (1999). Decrease in cortisol reverses human
hippocampal atrophy following treatment of Cushing’s disease. Bio-
logical Psychiatry, 46(12), 1595–1602.
Starkman, M. N., Giordani, B., Gebarski, S. S., & Schteingart, D. E.
(2003). Improvement in learning associated with increase in hip-
pocampal formation volume. Biological Psychiatry, 53(3), 233–238.
Steptoe, A., Siegrist, J., Kirschbaum, C., & Marmot, M. (2004). Effort-
reward imbalance, overcommitment, and measures of cortisol and
blood pressure over the working day. Psychosomatic Medicine,
66(3), 323–329.
Steptoe, A., & Willemsen, G. (2004). The inf luence of low job control on
ambulatory blood pressure and perceived stress over the working day
in men and women from the Whitehall II cohort. Journal of Hyperten-
sion, 22(5), 915–920.
Sterling, P., & Eyer, J. (1988). Allostatis: A new paradigm to explain
arousal pathology. In S. Fisher & J. Reason (Eds.), Handbook of life
stress, cognition and health (pp. 629–649). New York: Wiley.
Stern, J. M., Goldman, L., & Levine, S. (1973). Pituitary-adrenal respon-
siveness during lactation in rats. Neuroendocrinology, 12(3), 179–191.
Strauss, R. S. (2000). Adult functional outcome of those born small for ges-
tational age: Twenty-six-year follow-up of the 1970 British Birth Co-
hort. Journal of the American Medical Association, 283(5), 625–632.
Susman, E. J., Schmeelk, K. H., Worrall, B. K., Granger, D. A., Poni-
rakis, A., & Chrousos, G. P. (1999). Corticotropin-releasing hormone
and cortisol: Longitudinal associations with depression and anti-
social behavior in pregnant adolescents. Journal of the American
Academy of Child and Adolescent Psychiatry, 38(4), 460–467.
Suzuki, W. A., & Clayton, N. S. (2000). The hippocampus and memory:
A comparative and ethological perspective. Current Opinion in Neu-
robiology, 10(6), 768–773.
Szuran, T. F., Pliska, V., Pokorny, J., & Welzl, H. (2000). Prenatal stress
in rats: Effects on plasma corticosterone, hippocampal glucocorti-
coid receptors, and maze performance. Physiology and Behavior,
71(3/4), 353–362.
Takahashi, L. K. (1998). Prenatal stress: Consequences of glucocorti-
coids on hippocampal development and function. International Jour-
nal of Developmental Neuroscience, 16(3/4), 199–207.
Tang, C., Akabayashi, A., Manitiu, A., & Leibowitz, S. F. (1997). Hypo-
thalamic galanin gene expression and peptide levels in relation to cir-
culating insulin: Possible role in energy balance. Neuroendocrinology,
65(4), 265–275.

Taylor, S. E., Repetti, R. L., & Seeman, T. (1997). Health psychology:
What is an unhealthy environment and how does it get under the skin?
Annual Review of Psychology, 48, 411–447.
Teicher, M. H., Andersen, S. L., Polcari, A., Anderson, C. M., Navalta,
C. P., & Kim, D. M. (2003). The neurobiological consequences of
early stress and childhood maltreatment. Neuroscience Biobehavioral
Review, 27(1/2), 33–44.
Thomas, S. P., & Groer, M. W. (1986). Relationship of demographic,
life-style, and stress variables to blood pressure in adolescents. Nurs-
ing Research, 35(3), 169–172.
Torner, L., & Neumann, I. D. (2002). The brain prolactin system: Involve-
ment in stress response adaptations in lactation. Stress, 5(4), 249–257.
Torner, L., Toschi, N., Nava, G., Clapp, C., & Neumann, I. D. (2002). In-
creased hypothalamic expression of prolactin in lactation: Involve-
ment in behavioural and neuroendocrine stress responses. European
Journal of Neuroscience, 15(8), 1381–1389.
Toufexis, D. J., Thrivikraman, K. V., Plotsky, P. M., Morilak, D. A.,
Huang, N., & Walker, C. D. (1998). Reduced noradrenergic tone
to the hypothalamic paraventricular nucleus contributes to the
stress hyporesponsiveness of lactation. Journal of Neuroen-
docrinology, 10(6), 417–427.
Treisman, A. (1964). Monitoring and storage of irrelevant messages in
selective attention. Journal of Verbal Learning and Verbal Behavior,
3(6), 449–459.
Tulving, E. (2002). Episodic memory: from mind to brain. Annual Review
of Psychology, 53, 1–25.
Utsunomiya, H., Takano, K., Okazaki, M., & Mitsudome, A. (1999). Devel-
opment of the temporal lobe in infants and children: Analysis by MR-
based volumetry. American Journal of Neuroradiology, 20(4), 717–723.
Vallee, M., Mayo, W., Dellu, F., Le Moal, M., Simon, H., & Maccari, S.
(1997). Prenatal stress induces high anxiety and postnatal handling in-
duces low anxiety in adult offspring: Correlation with stress-induced
corticosterone secretion. Journal of Neuroscience, 17(7), 2626–2636.
Van Cauter, E., Polonsky, K. S., & Scheen, A. J. (1997). Roles of circa-
dian rhythmicity and sleep in human glucose regulation. Endocrine
Reviews, 18(5), 716–738.
van Goozen, S. H., Matthys, W., Cohen-Kettenis, P. T., Buitelaar, J. K.,
& van Engeland, H. (2000). Hypothalamic-pituitary-adrenal axis and
autonomic nervous system activity in disruptive children and
matched controls. Journal of the American Academy of Child and Ado-
lescent Psychiatry, 39(11), 1438–1445.
van Goozen, S. H., Matthys, W., Cohen-Kettenis, P. T., Thijssen, J. H., &
van Engeland, H. (1998). Adrenal androgens and aggression in con-
duct disorder prepubertal boys and normal controls. Biological Psy-
chiatry, 43(2), 156–158.
van Goozen, S. H., van den Ban, E., Matthys, W., Cohen-Kettenis, P. T.,
Thijssen, J. H., & van Engeland, H. (2000). Increased adrenal andro-
gen functioning in children with oppositional defiant disorder: A
comparison with psychiatric and normal controls. Journal of the Amer-
ican Academy of Child and Adolescent Psychiatry, 39(11), 1446–1451.
van Stegeren, A. H., Everaerd, W., Cahill, L., McGaugh, J. L., & Gooren,
L. J. (1998). Memory for emotional events: Differential effects of
centrally versus peripherally acting beta-blocking agents. Psy-
chopharmacology, 138(3/4), 305–310.
Vanyukov, M. M., Moss, H. B., Plail, J. A., Blackson, T., Mezzich, A. C.,
& Tarter, R. E. (1993). Antisocial symptoms in preadolescent boys
and in their parents: Associations with cortisol. Psychiatry Research,
46(1), 9–17.
Vargha-Khadem, F., Gadian, D. G., Watkins, K. E., Connelly, A., Van
Paesschen, W., & Mishkin, M. (1997). Differential effects of early
hippocampal pathology on episodic and semantic memory. Science,
277, 376–380.
References 627
Varney, N. R., Alexander, B., & MacIndoe, J. H. (1984). Reversible
steroid dementia in patients without steroid psychosis. American
Journal of Psychiatry, 141(3), 369–372.
Vevera, J., Zukov, I., Morcinek, T., & Papezova, H. (2003). Cholesterol
concentrations in violent and non-violent women suicide attempters.
European Psychiatry, 18(1), 23–27.
Virkkunen, M. (1979). Serum cholesterol in antisocial personality. Neu-
ropsychobiology, 5(1), 27–30.
Virkkunen, M., De Jong, J., Bartko, J., & Linnoila, M. (1989). Psychobi-
ological concomitants of history of suicide attempts among violent
offenders and impulsive fire setters. Archives of General Psychiatry,
46(7), 604–606.
Vythilingam, M., Heim, C., Newport, J., Miller, A. H., Anderson, E.,
Bronen, R., et al. (2002). Childhood trauma associated with smaller
hippocampal volume in women with major depression. American
Journal of Psychiatry, 159(12), 2072–2080.
Vythilingam, M., Vermetten, E., Anderson, G. M., Luckenbaugh, D., An-
derson, E. R., Snow, J., et al. (2004). Hippocampal volume, memory,
and cortisol status in major depressive disorder: Effects of treatment.
Biological Psychiatry, 56(2), 101–112.
Wadhwa, P. D., Sandman, C. A., Porto, M., Dunkel-Schetter, C., & Garite,
T. J. (1993). The association between prenatal stress and infant birth
weight and gestational age at birth: A prospective investigation.
American Journal of Obstetrics and Gynecology, 169(4), 858–865.
Walker, C. D., Lightman, S. L., Steele, M. K., & Dallman, M. F. (1992).
Suckling is a persistent stimulus to the adrenocortical system of the
rat. Endocrinology, 130(1), 115–125.
Walker, C. D., Trottier, G., Rochford, J., & Lavallee, D. (1995). Dissocia-
tion between behavioral and hormonal responses to the forced swim
stress in lactating rats. Journal of Neuroendocrinology, 7(8), 615–622.
Waters, M. A., & Lee, K. A. (1996). Differences between primigravidae
and multigravidae mothers in sleep disturbances, fatigue, and func-
tional status. Journal of Nurse-midwifery, 41(5), 364–367.
Weaver, I. C., Cervoni, N., Champagne, F. A., D’Alessio, A. C., Sharma,
S., Seckl, J. R., et al. (2004). Epigenetic programming by maternal
behavior. Nature Neuroscience, 7(8), 847–854.
Weingartner, H., Cohen, R. M., Murphy, D. L., Martello, J., & Gerdt, C.
(1981). Cognitive processes in depression. Archives of General Psy-
chiatry, 38(1), 42–47.
Weinstock, M. (1997). Does prenatal stress impair coping and regulation
of hypothalamic-pituitary-adrenal axis? Neuroscience and Biobehav-
ioral Reviews, 21(1), 1–10.
Welberg, L. A., & Seckl, J. R. (2001). Prenatal stress, glucocorticoids
and the programming of the brain. Journal of Neuroendocrinology,
13(2), 113–128.
Wellman, H. M., Cross, D., & Watson, J. (2001). Meta-analysis of theory-
of-mind development: The truth about false belief. Child Develop-
ment, 72(3), 655–684.
White, J. L., Moffitt, T. E., & Silva, P. A. (1989). A prospective replica-
tion of the protective effects of IQ in subjects at high risk for juve-
nile delinquency. Journal of Consulting and Clinical Psychology,
57(6), 719–724.
Wiesenfeld, A. R., Malatesta, C. Z., Whitman, P. B., Granrose, C., & Uili,
R. (1985). Psychophysiological response of breast- and bottle-feeding
mothers to their infants’ signals. Psychophysiology, 22(1), 79–86.
Windle, R. J., Brady, M. M., Kunanandam, T., Da Costa, A. P., Wilson,
B. C., Harbuz, M., et al. (1997). Reduced response of the hypothal-
amo-pituitary-adrenal axis to alpha1-agonist stimulation during lac-
tation. Endocrinology, 138(9), 3741–3748.
Windle, R. J., Wood, S., Shanks, N., Perks, P., Conde, G. L., Da Costa,
A. P., et al. (1997). Endocrine and behavioural responses to noise
628 Beyond the Stress Concept: Allostatic Load—A Developmental Biological and Cognitive Perspective
stress: Comparison of virgin and lactating female rats during non-
disrupted maternal activity. Journal of Neuroendocrinology, 9(6),
407–414.
Wing, R. R., Matthews, K. A., Kuller, L. H., Meilahn, E. N., & Plantinga,
P. (1991). Waist to hip ratio in middle-aged women: Associations with
behavioral and psychosocial factors and with changes in cardiovascu-
lar risk factors. Arteriosclerosis and Thrombosis, 11(5), 1250–1257.
Witek-Janusek, L. (1988). Pituitary-adrenal response to bacterial endo-
toxin in developing rats. American Journal of Physiology, 255(4, Pt.
1), E525–E530.
Wolf, O. T., & Kirschbaum, C. (1999). Actions of dehydroepiandros-
terone and its sulfate in the central nervous system: Effects on cogni-
tion and emotion in animals and humans. Brain Research Reviews,
30(3), 264–288.
Wolkowitz, O. M., Breier, A., Doran, A., Rubinow, D., Berrettini, W.,
Coppola, R., et al. (1988). Prednisone-induced behavioral and biolog-
ical changes in medically healthy volunteers. Psychopharmacology
Bulletin, 24(3), 492–494.
Wolkowitz, O. M., Reus, V. I., Canick, J., Levin, B., & Lupien, S. J. (1997).
Glucocorticoid medication, memory and steroid psychosis in medical
illness. Annals of the New York Academy of Sciences, 823, 81–96.
Wolkowitz, O. M., Reus, V. I., Weingartner, H., Thompson, K., Breier,
A., Doran, A., et al. (1990). Cognitive effects of corticosteroids.
American Journal of Psychiatry, 147(10), 1297–1303.
Wong, S. Y., Lau, E. M., Lynn, H., Leung, P. C., Woo, J., Cummings,
S. R., et al. (2005). Depression and bone mineral density: Is there a
relationship in elderly Asian men? Results from Mr. Os (Hong Kong).
Osteoporosis International, 16, 610–615.
Wright, B. E., Porter, J. R., Browne, E. S., & Svec, F. (1992). Antigluco-
corticoid action of dehydroepiandrosterone in young obese Zucker
rats. International Journal of Obesity and Related Metabolic Disor-
ders, 16(8), 579–583.
Wüst, S., Federenko, I., Hellhammer, D. H., & Kirschbaum, C. (2000).
Genetic factors, perceived chronic stress, and the free cortisol re-
sponse to awakening. Psychoneuroendocrinology, 25(7), 707–720.
Yakovlev, P. L., & Lecours, A. R. (1967). The myelogenetic cycles of re-
gional maturation of the brain. In A. Minkowski (Ed.), Regional de-
velopment of the brain in early life (pp. 3–70). Oxfort: Blackwell.
Yamada, K., Duong, D. T., Scott, D. K., Wang, J. C., & Granner, D. K.
(1999). CCAAT/enhancer-binding protein beta is an accessory factor
for the glucocorticoid response from the cAMP response element in
the rat phosphoenolpyruvate carboxykinase gene promoter. Journal of
Biological Chemistry, 274(9), 5880–5887.
Yeh, K. Y. (1984). Corticosterone concentrations in the serum and milk
of lactating rats: Parallel changes after induced stress. Endocrinol-
ogy, 115(4), 1364–1370.
Yehuda, R., Halligan, S. L., & Grossman, R. (2001). Childhood trauma
and risk for PTSD: Relationship to intergenerational effects of
trauma, parental PTSD, and cortisol secretion. Development and
Psychopathology, 13, 733–753.
Young, E. A., Aggen, S. H., Prescott, C. A., & Kendler, K. S. (2000). Sim-
ilarity in saliva cortisol measures in monozygotic twins and the inf lu-
ence of past major depression. Biological Psychiatry, 48(1), 70–74.